Drugs

, Volume 48, Issue 2, pp 297–326 | Cite as

Roxithromycin

An Update of its Antimicrobial Activity, Pharmacokinetic Properties and Therapeutic Use
  • Anthony Markham
  • Diana Faulds
Drug Evaluation

Abstract

Synopsis

Roxithromycin is a derivative of the macrolide antibacterial erythromycin with in vitro antibacterial activity resembling that of the parent compound. The drug has activity against some Staphylococcus spp., many Streptococcus spp., Moraxella (Branhamella) catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila and Chlamydia trachomatis as well as many less common organisms. Measured using recently proposed guidelines, roxithromycin has in vitro activity against Haemophilus influenzae. In comparison with that of its parent compound, the pharmacokinetic profile of roxithromycin is characterised by high plasma, tissue and body fluid concentrations and a long half-life permitting an extended dosage interval.

Roxithromycin has proven clinical efficacy in upper and lower respiratory infections, skin and soft tissue infections, urogenital infections and orodental infections, and appears to be as effective as more established treatments including erythromycin, amoxicillin/clavulanic acid and cefaclor. The drug has also shown promise in a variety of more specialised indications including opportunistic infections in human immunodeficiency virus (HlV)-positive patients and as part of a Helicobacter pylori eradication regimen. Roxithromycin is very well tolerated with an overall incidence of adverse events of approximately 4%.

Thus, roxithromycin is an attractive therapeutic alternative in its established indications, especially when the option of once-daily administration is considered.

Antibacterial Activity

Roxithromycin is an ether oxime derivative of erythromycin with in vitro activity resembling that of the parent compound. MIC90 (minimum concentration required to inhibit 90% of strains) values of ≤2 mg/L and 2 to 4 mg/L are indicative, respectively, of full and moderate susceptibility to the drug. Roxithromycin has variable activity against methicillin-susceptible Staphylococcus aureus but methicillin-resistant S. aureus, as well as S. epidermidis, S. haemolyticus and S. hominis, are not susceptible to the drug. Erythromycin-susceptible isolates of coagulase-negative staphylococci are susceptible to roxithromycin but erythro-mycin-resistant isolates are not.

Roxithromycin is active against Streptococcus agalactiae, S. pneumoniae, S. pyogenes, Lancefield group C and viridans group streptococci. It is generally inactive against Lancefield group G Streptococcus and enterococci. The activity of roxithromycin against Listeria monocytogenes is broadly similar to that of erythromycin, with most isolates being inhibited at a concentration of 1 or 2 mg/L.

Roxithromycin MIC90 values for Neisseria gonorrhoeae are similar to those of erythromycin; Neisseria meningitidis is slightly less susceptible with an MIC range of 0.3 to 4 mg/L.

Roxithromycin has borderline activity in vitro against Haemophilus influenzae when measured using current susceptibility guidelines; however, a higher susceptibility breakpoint of ≤16 mg/L has recently been proposed. The drug has good in vitro activity against Bordetella pertussis, B. parapertussis, Borrelia burgdorferi, Moraxella catarrhalis and Legionella pneumophila. Roxithromycin MIC90 values against Chlamydia trachomatis range between 0.25 and 1 mg/L.

Roxithromycin had an MIC90 value of 16 mg/L against 28 Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome, compared with values of 8, 32 and ≥64 mg/L for clarithromycin, azithromycin and erythromycin, respectively.

Roxithromycin MIC90 values against Bacteroides spp. and Clostridium difficile are high.

Roxithromycin exerts its action by disrupting bacterial protein synthesis. It is also concentrated in human polymorphonuclear leucocytes and macrophages. The drug has demonstrated good activity in animal models of Gram-positive and other infections such as toxoplasma encephalitis, Legionnaires’ disease, Mycobacterium leprae infection, syphilis and chlamydial urogenital infection.

Pharmacokinetic Prapertics

The pharmacokinetic profile of roxithromycin differs substantially from that of its parent compound, erythromycin.

Mean plasma roxithromycin concentrations ranging between 6.6 and 7.9 mg/L are achieved within 2 hours after administration of a single oral 150mg dose. In a direct comparison, the area under the plasma concentration versus time curve produced by roxithromycin 150mg was 16.2-fold greater than that produced by erythromycin 250mg. Multiple doses produced similar differences. The drug is strongly, specifically and saturably bound to a 1-acid glycoprotein in plasma. The plasma clearance of roxithromycin appears to be dose- or plasma concentration-dependent. Concentrations achieved in tissues and body fluids are generally higher than MIC90 values for susceptible organisms. In a study assessing elimination, 74.2% of a radiolabeled roxithromycin dose was accounted for: 53.4% in faeces; 13.4% as expired carbon dioxide and 7.4% in the urine.

The mean elimination half-life of roxithromycin (8.4 to 15.5 hours) is much longer than that recorded for erythromycin (1.5 to 3 hours). Its pharmacokinetics appear to be nonlinear and may include a saturable process involving plasma a 1-acid glycoprotein releasing bound drug for distribution and elimination.

The pharmacokinetic profile of roxithromycin in children is generally similar to that in adults. Dosage adjustment is not required in the elderly or in patients with renal impairment.

Therapeutic Use

Roxithromycin has produced efficacy rates of between 71 and 96% in patients with tonsillitis or sinusitis and resolved or improved the signs and symptoms of pharyngotonsillitis and sinusitis significantly more effectively than clarithromycin in 1 study.

Clinical efficacy rates were >90% in almost 10 000 patients with acute bronchitis who received roxithromycin in noncomparative studies. The clinical efficacy of roxithromycin was very similar to that of amoxicillin/clavulanic acid, cefaclor and azithromycin in comparative studies. Roxithromycin is also an effective treatment for exacerbations of chronic bronchitis, producing clinical efficacy rates ranging between 83.3 and 89% in 4 noncomparative trials involving >4000 patients, and having clinical efficacy similar to that of amoxicillin/clavulanic acid, oxycycline, cefaclor and azithromycin in comparative studies.

Roxithromycin has demonstrated similar clinical efficacy to amoxicillin/clavulanic acid, azithromycin, clarithromycin, cefaclor, erythromycin and midecamycin acetate in patients with pneumonia. The drug is also an effective treatment for patients with pneumonia caused by atypical organisms such as chlamydia, mycoplasma, Legionella spp., rickettsia and Coxiella burnetii.

Roxithromycin 300 mg/day was equally effective administered either once or twice daily to 1588 patients with various infections.

One study has shown roxithromycin to be as effective as josamycin as treatment for patients with suppurative skin and soft tissue infections and as effective as penicillin in patients with erysipelas.

The clinical efficacy of roxithromycin was similar to that of amoxicillin, erythromycin and josamycin as treatment for orodental and odontological infections and was also comparable with spiramycin as prophylaxis prior to dental surgery.

In patients with urogenital or gynaecological infections, roxithromycin has produced clinical response rates ranging between 71 and 100%, and was as effective as doxycycline and minocycline in comparative studies. The drug was equally effective administered either once or twice daily in patients with nongonococcal urethritis.

Roxithromycin has good in vitro activity against Borrelia burgdorferi and, in combination with cotrimoxazole (trimethoprim/sulfamethoxazole), was an effective treatment for late Lyme disease. In a pilot study the drug effectively prevented pneumocystosis and cerebral toxoplasmosis in human immunodeficiency virus (HlV)-positive patients, either alone or in combination with pentamidine aerosol. Roxithromycin 300 mg/day in combination with omeprazole and bismuth subni-trate eradicated confirmed Helicobacter pylori infection in patients with peptic ulcers and gastritis more effectively than omeprazole monotherapy.

Although recent paediatric studies are limited, roxithromycin 5 to 10 mg/kg/day has demonstrated efficacy in the treatment of respiratory tract and skin and soft tissue infections in children and, compared with placebo, has significantly reduced the duration of diarrhoea and faecal excretion of Campylobacter in children with campylobacter-associated enteritis.

Tolerability

Gastrointestinal symptoms are the most common adverse events during roxithromycin therapy. Large noncomparative studies have reported an overall incidence of adverse events of around 4%, with gastrointestinal symptoms accounting for 75 to 80% of these. The overall incidence of adverse events in patients treated with roxithromycin has compared favourably with those of other antibacterial drugs and appears to be lower than that of erythromycin. The adverse event profile of the drug in children is similar to that in adults.

Isolated cases of cholestatic hepatitis and 1 case of fulminant acute hepatitis have been reported in patients receiving roxithromycin.

The drug appears to have less effect on gastrointestinal motility and faecal bacterial flora than erythromycin.

Dosage and Administration

Roxithromycin 300 mg/day, administered once-daily or in 2 divided doses, is the recommended adult dosage for all indications. The recommended dose for infants and children is 5 to 8 mg/kg body weight per day administered in 2 divided doses. The drug should be given at least 15 minutes before food. A 50% dosage reduction has been recommended for patients with hepatic insufficiency. Dosage modifications are not required in elderly patients or in patients with renal insufficiency.

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References

  1. 1.
    Young RA, Gonzalez JP, Sorkin EM. Roxithromycin: a review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs 1989; 37: 8–41PubMedCrossRefGoogle Scholar
  2. 2.
    Jones RN. Disk diffusion susceptibility testing of macrolides: the interpretive criteria. In: Bryskier AJ, Butzler J-P, Neu HC, et al., editors. Macrolides: chemistry, pharmacology and clinical uses. Paris: Arnette Blackwell, 1993: 209–15Google Scholar
  3. 3.
    Erwin ME, Jones RN. Roxithromycin in-vitro susceptibility testing of Haemophilus influenzae by NCCLS methods. J Antimicrob Chemother 1993; 32: 652–4PubMedCrossRefGoogle Scholar
  4. 4.
    Barry AL, Thornsberry C, Jones RN. In vitro activity of a new macrolide, A-56268, compared with that of roxithromycin, erythromycin and clindamycin. Antimicrob Agents Chemo ther 1987; 31: 343–5CrossRefGoogle Scholar
  5. 5.
    Barry AL. In vitro potency of nine orally administered antimicrobial agents against three respiratory tract pathogens. Eur J Clin Microbiol Infect Dis 1992; 11: 867–9PubMedCrossRefGoogle Scholar
  6. 6.
    Bergeron MG, Lavoie GY, Boucher FDW. Comparative bactericidal activity of Cefixime, carumonam, enoxacin and roxithromycin with those of other antibiotics against resistant Haemophilus influenzae including β-lactam tolerant strains. J Antimicrob Chemother 1987; 20: 663–9PubMedCrossRefGoogle Scholar
  7. 7.
    Bowie WR, Shaw CE, Chan DGW, et al. In vitro activity of Ro 15-8074, Ro 19-5247, A-56268 and roxithromycin (RU 28965) against Neisseria gonorrhoeae and Chlamydia trachomatis. Antimicrob Agents Chemother 1987; 31: 470–2PubMedCrossRefGoogle Scholar
  8. 8.
    Casal Roman M, Gutierrez Aroca J, Ruiz Martinez P, et al. In vitro activity of macrolides alone and in combination with antituberculous compounds against Mycobacterium tuberculosis. Rev Esp Quimioter 1990; 3: 69–72Google Scholar
  9. 9.
    Chardon H, Bellon O, Bourgeous F, et al. Comparative in vitro activity of five macrolides against 190 strains of Branhamella catarrhalis [in French]. Pathol Biol 1989; 37: 382–5PubMedGoogle Scholar
  10. 10.
    Chuard C, Rohner P, Dunand V. In-vitro and in-vivo evaluation of the antistaphylococcal activity of S-5556, a new 16-membered macrolide. J Antimicrob Chemother 1992; 30: 327–37PubMedCrossRefGoogle Scholar
  11. 11.
    Dailloux M, Villemain P. Bacteriostatic and bactericidal activities of cyclines, macrolides, and fluoroquinolones against Chlamydia trachomatis. Pathol Biol 1992; 40: 455–60PubMedGoogle Scholar
  12. 12.
    Dutilh B, de Barbeyrac B, Lafferrière C, et al. Activité comparée in vitro d’un nouveau macrolide RU 28965 et de l’eryth-romycycine vis-à-vis de Chlamydia trachomatis. Pathol Biol 1986; 34: 445–7PubMedGoogle Scholar
  13. 13.
    Endtz HP, Broeren M, Mouton RP. In vitro susceptibility of quinolone-resistant Campylobacter jejuni to new macrolide antibiotics. Eur J Clin Microbiol Infect Dis 1993; 12: 48–50PubMedCrossRefGoogle Scholar
  14. 14.
    Felmingham D, Robbins MJ, Sanghrajka M, et al. The in vitro activity of some 14-, 15- and 16- membered macrolides against Staphylococcus spp., Legionella spp., Mycoplasma spp. and Ureaplasma urealyticum. Drugs Exp Clin Res 1991; 17: 91–9, No. 1Google Scholar
  15. 15.
    Ferreruela RM, Alcaraz MJ, Farga MA, et al. Activity of new macrolides against genitourinary and respiratory mycoplasmas. Rev Esp Quimioter 1991; 4: 209–15Google Scholar
  16. 16.
    Garcia-Rodriguez JA, Garcia Sanchez JE, Garcia Garcia MI, et al. In vitro activities of new oral β-lactams and macrolides against Camphylobacter pylori. Antimicrob Agents Chemother 1989; 33: 1650–1PubMedCrossRefGoogle Scholar
  17. 17.
    Goldstein FW, Emirian MF, Coutrot A, et al. Bacteriostatic and bactericidal activity of azithromycin against Haemophilus in fluenzae. J Antimicrob Chemother 1990; 25 Suppl. A: 25–8PubMedCrossRefGoogle Scholar
  18. 18.
    Hardy DJ, Hensey DM, Beyer JM, et al. Comparative in vitro activities of new 14-, 15-, and 16-membered macrolides. Antimicrob Agents Chemother 1988; 32: 1710–9PubMedCrossRefGoogle Scholar
  19. 19.
    Hoppe JE, Eichhorn A. Activity of new macrolides against Bordatella pertussis and Bordatella parapertussis. Eur J Clin Microbiol Infect Dis 1989; 8: 653–4PubMedCrossRefGoogle Scholar
  20. 20.
    Liebers DM, Baltch AL, Smith RP, et al. Susceptibility of Legionella pneumophila to eight antimicrobial agents including four macrolides under different assay conditions. J Antimicrob Chemother 1989; 23: 37–41PubMedCrossRefGoogle Scholar
  21. 21.
    Loza E, Martinez Beltrán J, Baquero F, et al. Comparative in vitro activity of clarithromycin. New Antimicrobial Agents 1992; 11: 856–66Google Scholar
  22. 22.
    Neu HC, Chin N-x, Gu J-w. The in-vitro activity of new streptogramins, RP 59500, RP 57669 and RP 54476, alone and in combination. J Antimicrob Chemother 1992; 30 (A Suppl.): 83–94PubMedCrossRefGoogle Scholar
  23. 23.
    Rolston KV, Ho DH, LeBlanc B. Comparative in vitro activity of the new erythromycin derivative dirithromycin against Gram-positive bacteria isolated from cancer patients. Eur J Clin Microbiol 1990; 9: 30–3CrossRefGoogle Scholar
  24. 24.
    Sefton AM, Maskell JP, Yong FJ, et al. Comparative in vitro activity of A-56268. Eur J Clin Microbiol Infect Dis 1988; 7: 798–802PubMedCrossRefGoogle Scholar
  25. 25.
    Spencer RC, Wheat PF. In vitro activity of roxithromycin against Moraxella catarrhalis. Diagn Microbiol Infect Dis 1992; 15 Suppl. 4: 63S–5SPubMedCrossRefGoogle Scholar
  26. 26.
    Kern W, Linzmeier K, Kurrle E. Antimicrobial susceptibility of viridans group streptococci isolated from patients with acute leukemia receiving ofloxacin for antibacterial prophylaxis. Infection 1989; 17: 396–7PubMedCrossRefGoogle Scholar
  27. 27.
    Le Noc P, Croize J, Bryskier A, et al. Comparative in vitro bacteriostatic and bactericidal activities of five macrolides (roxithromycin, erythromycin, troleandomycin, josamycin, spiramycin) against 284 hospital bacterial strains [in French]. Pathol Biol 1989; 37: 553–9PubMedGoogle Scholar
  28. 28.
    Suermondt G, Denamur E, Fleuret A, et al. In vitro activity of miocamycin compared with pristinamycin and four macrolides on B. catarrhalis (French). Pathol Biol 1989; 37: 386–9PubMedGoogle Scholar
  29. 29.
    Jones RN, Barry AL, Thornsberry C. In vitro evaluation of three new macrolide antimicrobial agents, RU 28965, RU 29065 and RU 29702, and comparisons with other orally administered drugs. Antimicrob Agents Chemother 1983; 24: 209–15PubMedCrossRefGoogle Scholar
  30. 30.
    Fleurette J, Bornstein N. Susceptibility of Legionella species to roxithromycin [abstract]. 15th International Congress of Chemotherapy; 1987 Jul 19–24: IstanbulGoogle Scholar
  31. 31.
    Fournet M-P, Zini R, Deforges L, et al. Determination of binding parameters of macrolides, lincosamides, and streptogramins to Legionella pneumophila. J Pharm Sei 1987; 76: 153–6CrossRefGoogle Scholar
  32. 32.
    Hara K, Suyama N, Yamaguchi K, et al. Activity of macrolides against organisms responsible for respiratory infection with emphasis on Mycoplasma and Legionella. J Antimicrob Chemother 1987; 20 Suppl. B: 75–80PubMedCrossRefGoogle Scholar
  33. 33.
    Jones RN, Erwin ME. Review of the anti-legionella activity of roxithromycin and the use of the E-test to determine potency [abstract]. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  34. 34.
    Acar JF, Goldstein FW. In vitro activity against Gram-positive and Gram-negative bacteria. In: Neu HC, Young LS, Zinner SH, editors. The new macrolides, azalides and streptogramins. Pharmacology and clinical applications. New York: Marcel Dekker, Inc., 1993: 13–24Google Scholar
  35. 35.
    Tomé G, Goldberg M, Jugo M, et al. Bacteriostatic and bactericidal activity of roxithromycin against H. influenazae (Hi) isolated from patients suffering respiratory tract infections (RTI) [abstract]. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  36. 36.
    Struelens MJ, Nonhoff C, Lontie M, et al. In vitro activity of commonly used oral antimicrobial agents against community isolates of respiratory pathogens. Acta Clin Belg 1991; 46: 283–9PubMedGoogle Scholar
  37. 37.
    Soussy CJ, Chanal M, Kitzis MD, et al. In vitro antibacterial activity of roxithromycin for hospital bacteria and regression curve [in French]. Pathol Biol 1988; 36: 420–4PubMedGoogle Scholar
  38. 38.
    Barlam T, Neu HC. In vitro comparison of the activity of RU28965. a new macrolide, with that of erythromycin against aerobic and anaerobic bacteria. Antimicrob Agents Chemo ther 1984; 25: 529–31Google Scholar
  39. 39.
    Casellas JM, Goldberg M, Arduiros S, et al. Comparative MIC and MBC of roxithromycin, A56286 and erythromycin against 600 clinical isolates [abstract]. 15th International Congress of Chemotherapy; 1987 Jul 19–24Google Scholar
  40. 40.
    Croize J, Le Noc P, Bryskeir A, et al. Activité in vitro de trois macrolides: érythromycine, josamycine et roxithromycine vis-a-vis de 349 bactéries aérobies ou anaérobies. Bordeaux Médical 1987; 20: 159–62Google Scholar
  41. 41.
    King A, Phillips I. The in vitro activity of roxithromycin, a new macrolide antibiotic, in comparison with that of erythromycin. Drugs Exp Clin Res 1987; 13: 563–6PubMedGoogle Scholar
  42. 42.
    Tsuboi Y, Sakoda T, Mitsuhashi S. In vitro and in vivo antibacterial activity of roxithromycin. Br J Clin Pract 1988; 42 Suppl. 55: 30–2Google Scholar
  43. 43.
    Kurzynski TA, Boehm DM, Rott-Petri JA, et al. ntimicrobial susceptibilities of Bordetella species isolated in a multicenter pertussis surveillance project. Antimicrob Agents Chemother 1988; 32: 137–40PubMedCrossRefGoogle Scholar
  44. 44.
    Preac-Mursic V, Wilske B, Schierz G, et al. Comparative antimicrobial activity of the new macrolides against Borrelia burgdorferi. European Journal of Clinical Microbiology and Infectious Disease 1989; 8: 651–3CrossRefGoogle Scholar
  45. 45.
    Gasser R, Reisinger E, Klein W. Combined therapy with roxithromycin and co-trimoxazole of late Lyme disease [abstract no. 5103]. 18th International Congress of Chemotherapy; 1993 Jun 27–Jul; Stockholm: 401Google Scholar
  46. 46.
    Hansen K, Hovmark A, Lebech A-M, et al. Roxithromycin in Lyme borreliosis: discrepant results of an in vitro and in vivo animal susceptibility study and a clinical trial in patients with erythema migrans. Acta Derm Venereol 1992; 72: 297–300PubMedGoogle Scholar
  47. 47.
    Sambri V, Massaria F, Cevenini R, et al. In-vitro susceptibility of Borrelia burgdorferi and Borrelia hermsii to ten antimicro bial agents. J Chemother 1990; 2: 348–50PubMedGoogle Scholar
  48. 48.
    Murray DM, DuPont HL, Cooperstock M, et al. Evaluation of new anti-infective drugs for the treatment of gastritis and peptic ulcer disease associated with infection by Helicobacter pylori. Clin Infect Dis 1992; 15 Suppl. 1: S268–73PubMedCrossRefGoogle Scholar
  49. 49.
    Marelli P, Di Campli E, Campa M, et al. In vitro activity of macrolides and omeprazole against Helicobacter pylori [ab-stract no. 265]. 6th European Congress of Clinical Microbiology and Infectious Diseases; 1993 Mar 28–31; Seville, 1993Google Scholar
  50. 50.
    Dubreuil L. In vitro comparison of roxithromycin and erythromycin against 900 anaerobic bacterial strains. J Antimicrob Chemother 1987; 20 Suppl. B: 13–9PubMedCrossRefGoogle Scholar
  51. 51.
    Rastogi N, Goh KS, Bryskier A. In vitro activity of roxithromycin against 16 species of atypical mycobacteria and effect of pH on its radiometric MICs. Antimicrob Agents Chemother 1993; 37: 1560–2PubMedCrossRefGoogle Scholar
  52. 52.
    Naik S, Ruck R. In vitro activities of several new macrolide antibiotics against Mycobacterium avium complex. Antimicrob Agents Chemother 1989; 33: 1614–6PubMedCrossRefGoogle Scholar
  53. 53.
    Casai M, Rodriguez F, Villalba R, et al. In vitro usceptibility of Mycobacterium avium-complex against rifabutin (LM 427) alone and in combination with amikacin, roxithromycin and ethambutol. Rev Esp Quimioter 1990; 3: 87–9Google Scholar
  54. 54.
    Rastogi N, Seng Goh K, Bryskier A. Activity of roxithromycin used alone and in combination with ethambutol, rifampin, amikacin, ofloxacin and clofazimine against the Mycobacterium avium complex [abstract]. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  55. 55.
    Brown BA, Wallace Jr RJ, Onyi GO, et al. Activities of four macrolides, including clarithromycin, against Mycobacterium fortuitum, Mycobacterium chelonae, and M. chelonaelike organisms. Antimicrob Agents Chemother 1992; 36: 180–4CrossRefGoogle Scholar
  56. 56.
    Forsgren A. Antibiotic susceptibility of Mycobacterium marinum. Scand J Infect Dis 1993; 25: 779–82, No.6PubMedCrossRefGoogle Scholar
  57. 57.
    Cevenini R, Rumpianesi F, Sambri V, et al. In vitro activity of RU 28965, a new macrolide, against Chlamydia trachomatis and Ureaplasma urealyticum. In Butzler & Kobayashi (Eds) 1986.; Macrolides: a review with an outlook on future developments, p. 125–127, Excerpta Medica, AmsterdamGoogle Scholar
  58. 58.
    Stamm WE, Suchland R. Antimicrobial activity of U-70138 F (paldimycin), roxithromycin (RU 965), and ofloxacin (ORF 18489) against Chlamydia trachomatis in cell culture. Antimicrob Agents Chemother 1986; 30: 806–7PubMedCrossRefGoogle Scholar
  59. 59.
    Rumpianesi F, Morandotti G, Sperning R, et al. In vitro activity of azithromycin against Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis in comparison with erythromycin, roxithromycin and minocycline. J Chemother 1993; 5: 155–8PubMedGoogle Scholar
  60. 60.
    Ridgway GL, Mumtaz G, Fenelon L, et al. The in-vitro of clarithromycin and other macrolides against the type strain of Chlamydia pneumoniae (TWAR). J Antimicrob Chemother 1991; 27 Suppl. A: 43–5PubMedCrossRefGoogle Scholar
  61. 61.
    Cuffini AM, Tullio V, Cimino F, et al. Comparative effects of roxithromycin and erythromycin on cellular immune functions in vitro. 1 uptake of 3H-macrolides by human macrophages. Microbios 1989; 57: 167–78Google Scholar
  62. 62.
    Hand WL, King-Thompson N, Holman JW. Entry of roxithromycin (RU 965), imipenem, cefotaxime, trimethoprim and metronidazole into human polymorphonu-clear leukocytes. Antimicrob Agents Chemother 1987; 31: 1553–7PubMedCrossRefGoogle Scholar
  63. 63.
    Hand WL, King-Thompson NL. The entry of antibiotics into human monocytes. J Antimicrob Chemother 1989; 23: 681–9PubMedCrossRefGoogle Scholar
  64. 64.
    Ishiguro M, Koga H, Kohno S, et al. Penetration of macrolides into human polymorphonuclear leucocytes. J Antimicrob Chemother 1989; 24: 719–29PubMedCrossRefGoogle Scholar
  65. 65.
    Fietta A, Boeri P, Colombo ML. Bioactivity of flurithromycin and other macrolides against intracellular susceptible staphylococci. Chemotherapy Basel 1993; 39: 48–54CrossRefGoogle Scholar
  66. 66.
    Torigoe R. The intracellular activity of ofloxacin and roxithromycin against Staphylococcus aureus phagocytosed in human neutrophils. Chemotherapy Tokyo 1993; 41: 955–62Google Scholar
  67. 67.
    Hamilton-Miller JMT, Shah S. Post-antibiotic effects of miocamycin, roxithromycin and erythromycin on gram-positive cocci. Int J Antimicrob Agents 1993; 2: 105–9, FebPubMedCrossRefGoogle Scholar
  68. 68.
    Kuenzi B, Segessenman C, Gerber AU. Postantibiotic effect of roxithromycin, erythromycin, and clindamycin against seected Gram-positive bacteria and Haemophilus influenzae. J Antimicrob Chemother 1987; 20 Suppl. B: 39–46PubMedCrossRefGoogle Scholar
  69. 69.
    Rolin O, Bouanchaud DH. Comparison of in vitro post-antibiotic effect induced by 14-membered-ring macrolides (erythromycin and roxithromycin) and 16-membered-ring macrolides (josamycin and spiramycin) in Staphylococcus aureus [in French]. Pathol Biol 1989; 37: 375–7PubMedGoogle Scholar
  70. 70.
    Odenholt-Tornqvist I, Löwdin E, Cars O. Postantibiotic sub- MIC effects of vancomycin, roxithromycin, Sparfloxacin, and amikacin. Antimicrob Agents Chemother 1992; 36: 1852–8PubMedCrossRefGoogle Scholar
  71. 71.
    Moneib NA, Shibl AM, El-Said MA, et al. Macrolides induced suppression of virulence factors produced by Staphylococcus aureus. J Chemother 1993; 5: 289–92PubMedGoogle Scholar
  72. 72.
    Paulsen O. Roxithromycin — a macrolide with improved phar macokinetic properties. Drugs Today 1991; 27: 193–222Google Scholar
  73. 73.
    Carlone NA, Cuffini AM, Tullio V, et al. Comparative effects of roxithromycin and erythromycin on cellular immune functions in vitro. 2 Chemotaxis and phagocytosis of 3-Staphylococcus aureus by human macrophages. Microbios 1989; 58: 17–25Google Scholar
  74. 74.
    Anderson R. Erythromycin and Roxithromycin potentiate human neutrophil locomotion in vitro by inhibition of leukoattractant-Activated superoxide generation and autoox-idation. J Infect Dis 1989; 159: 966–73PubMedCrossRefGoogle Scholar
  75. 75.
    Satake N, Nagai S, Nishimura K, et al. The effect of roxithromycin (RXM, erythromycin derivative) on blood neutrophil mobility toward FMLP in patients with diffuse bronchiectasis and idiopathic pulmonary fibrosis. Eur Respir J 1992; 5 Suppl. 15: 142Google Scholar
  76. 76.
    Akamatsu H, Sasaki H, Matoba Y, et al. Effects of roxithromycin on neutrophil Chemotaxis and phagocytosis in vitro. Ensho 1994; 14: 59–65CrossRefGoogle Scholar
  77. 77.
    Bailly S, Pocidalo J-J, Fay M, et al. Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin. Antimicrob Agents Chemother 1991; 35: 2016–9PubMedCrossRefGoogle Scholar
  78. 78.
    Lianou PE, Bassaris HB, Vlachodimitropoulos D, et al. Inter actions of subinhibitory concentrations of roxithromycin with Gram-positive bacteria [abstract]. 16th International Congress of Chemotherapy; 1989 Jun 11–16: JerusalemGoogle Scholar
  79. 79.
    Zana J, Muffat-Joly M, Thomas D, et al. Roxithromycin treat ment of mouse chlamydial salpingitis and protective effect on fertility. Antimicrob Agents Chemother 1991; 35: 430–5PubMedCrossRefGoogle Scholar
  80. 80.
    Lukehart SA, Baker-Zander SA. Roxithromycin (RU 965): effective therapy for experimental syphilis infection in rabbits. Antimicrob Agents Chemother 1987; 31: 187–90PubMedCrossRefGoogle Scholar
  81. 81.
    Fitzgeorge RB, Featherstone ASR. Roxithromycin therapy of experimental Legionnaires’ disease. Correspondence. J Antimicrob Chemother 1989; 23: 462–3CrossRefGoogle Scholar
  82. 82.
    Jayais P, Pangon B, Valois JM, et al. Activity of roxithromycin in prophylactic treatment of experimental Staphylococcus aureus endocarditis [abstract]. 16th International Congress of Chemotherapy; 1989 Jun 11–16: Jerusalem: 108Google Scholar
  83. 83.
    Calame W, Guiot HFL, Mattie H. Influence of cytostatic treatment on the efficacy of erythromycin and roxithromycin in a staphylococcal infection in mice. Scand J Infect Dis 1990; 22: 717–23, No.6PubMedCrossRefGoogle Scholar
  84. 84.
    Franzblau SG, Hastings RC. In vitro and in vivo activities of macrolides against Mycobacterium leprae. Antimicrob Agents Chemother 1988; 32: 1758–62PubMedCrossRefGoogle Scholar
  85. 85.
    Gelber RH, Siu P, Tsang M, et al. Activities of various macrolide antibiotics against Mycobacterium leprae infection in mice. Antimicrob Agents Chemother 1991; 35: 760–3PubMedCrossRefGoogle Scholar
  86. 86.
    Luft BJ. In vivo and in vitro activity of roxithromycin against Toxoplasma gondii in mice. European Journal of Clinical Microbiology 1987; 6: 479–81PubMedCrossRefGoogle Scholar
  87. 87.
    Luft BJ, Hofflin J, Chen J, et al. The activity of RU 28965, a macrolide, in the treatment of toxoplasmic encephalitis [abstract]. Interscience Congress on Antimicrobial Agents and Chemotherapy; 1986; New OrleansGoogle Scholar
  88. 88.
    Chang HR, Pechère JC. Activity of the combination of pyrimethamine plus roxithromycin on Toxoplasma gondii in mice. 16th International Congress of Chemotherapy; 1989 Jun 11–16: Jerusalem: 22Google Scholar
  89. 89.
    Chang HR, Pechère J-CF. In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin [CP-62,993], and A-562268) on Toxoplasma gondii. Antimicrob Agents Chemother 1988; 32: 524–9PubMedCrossRefGoogle Scholar
  90. 90.
    Kees F, Grobecker H, Fourtillian JB, et al. Comparative pharmacokinetics of single dose roxithromycin (150mg) versus erythromycin stéarate (500mg) in healthy volunteers. Br J Clin Pract 1988; 42 Suppl. 55: 51Google Scholar
  91. 91.
    Puri SK, Lassman HB. Roxithromycin: a pharmacokinetic review of a macrolide. J Antimicrob Chemother 1987; 20 Suppl B.: 89–100PubMedCrossRefGoogle Scholar
  92. 92.
    Zini R, Fournet MP, Barre J, et al. In vitro study of roxithromycin binding to serum proteins and erythrocytes in humans. Br J Clin Pract 1988; 42 Suppl. 55: 54Google Scholar
  93. 93.
    Lassman HB, Puri SK, Ho I, et al. Pharmacokinetics of Roxithromycin (RU 965). J Clin Pharmacol 1988; 28: 141–52PubMedGoogle Scholar
  94. 94.
    Nilsen OG, Aamo T, Zahlsen K, et al. Macrolide pharmacokinetics and dose scheduling of roxithromycin. Diagn Microbiol Infect Dis 1992; 15 Suppl. 4: 71S–6SPubMedCrossRefGoogle Scholar
  95. 95.
    Boeckh M, Lode H, Höffken G. Pharmacokinetics of roxithromycin and influence of H2-blockers and antacids on gastrointestinal absorption. Eur J Clin Microbiol Infect Dis 1992; 11: 465–8PubMedCrossRefGoogle Scholar
  96. 96.
    Tremblay D, Meyer B, Saint-Salvi B, et al. Influence of food on bioavailability of roxithromycin (RU 28 965). Acta Phar-acologica et Toxicologica 1986; 59 Suppl. 5: 191Google Scholar
  97. 97.
    Anonymous. Roxithromycin prescribing information. AustraliaGoogle Scholar
  98. 98.
    98. Birkett DJ, Robson RA, Grgurinovich N, et al. Single oral dose pharmacokinetics of erythromycin and roxithromycin and the effects of chronic dosing. Ther Drug Monit 1990; 12: 65–71PubMedCrossRefGoogle Scholar
  99. 99.
    Acar JF, Saint-Salvi B, Blanc F. Concentration of roxithromycin in tear fluid and saliva after repeat dosing. Br J Clinract 1988; 42 Suppl. 55: 82Google Scholar
  100. 100.
    Begue P, Lacome H, Cotin G, et al. Diffusion of roxithromycin into tonsillar tissue in children. Br J Clin Pract 1988; 42 Suppl. 55: 78–9Google Scholar
  101. 101.
    Botto H, Carney M, Chretien P, et al. Study of the diffusion of roxithromycin into prostatic tissue after repeat oral dosing. Br J Clin Pract 1988; 42 Suppl. 55: 83Google Scholar
  102. 102.
    Campa M, Zolfino I, Senesi S, et al. The penetration of roxithromycin into human skin. J Antimicrob Chemother 1990; 26: 87–90PubMedCrossRefGoogle Scholar
  103. 103.
    De Grandi P, Comte R, Von Moos G, et al. Concentration of roxithromycin in plasma and gynaecological tissues following repeated oral administrations. Br J Clin Pract Symp Suppl 1988; 42 Suppl. 55: 84–5Google Scholar
  104. 104.
    Kafetzis DA, Ligatsikas C, Saint-Salvi B, et al. Concentrations of roxithromycin in tonsil and adenoid tissues after single and repeated administrations to children. Br J Clin Pract 1988; 42 Suppl. 55: 80Google Scholar
  105. 105.
    Meirovich CI, Monkrull H, Strusberg AM, et al. Roxithromycin levels in synovial fluid. Br J Clin Pract 1988; 42 Suppl. 55: 88Google Scholar
  106. 106.
    Rimoldi R, Mangiarotti P, De Rose V, et al. Penetration of roxithromycin into bronchial secretions. Br J Clin Pract 1988; 42 Suppl. 55: 74–7Google Scholar
  107. 107.
    Tremblay D, Mignot A, Couraud L, et al. Concentrations of roxithromycin in lung tissue after repeat dosing. Br J Clin Pract 1988; 42 Suppl. 55: 73Google Scholar
  108. 108.
    Boccazzi A, Langer M. Penetration of roxithromycin into bronchial secretions. Chemotherapy Basel 1991; 37: 303–9CrossRefGoogle Scholar
  109. 109.
    Vandeghen P, Smets P, Gerardy B, et al. Penetration of roxithromycin into the gastric mucosa [abstract]. 16th International Congress of Chemotherapy; 1989 Jun 11–16: Jerusalem: 222Google Scholar
  110. 110.
    Del Tacca M, Danesi R, Bernadini N, et al. Roxithromycin penetration into gingiva and alveolar bone of odontoiatric patients. Chemotherapy Basel 1990; 36: 332–6CrossRefGoogle Scholar
  111. 111.
    McLean A, Sutton JA, Salmon J, et al. Roxithromycin: pharmacokinetic and metabolism study in humans. Br J Clin Pract 1988; 42 Suppl. 55: 52–3Google Scholar
  112. 112.
    Wise R, Kirkpatrick B, Ashby J, et al. Pharmacokinetics and tissue penetration of roxithromycin after multiple dosing. Antimicrob Agents Chemother 1987; 31: 1051–3PubMedCrossRefGoogle Scholar
  113. 113.
    Tremblay D, Jaeger H, Fourtillan JB, et al. harmacokinetics of three single doses (150, 300, 450mg) of roxithromycin in young volunteers. Br J Clin Pract 1988; 42 Suppl. 55: 49–50Google Scholar
  114. 114.
    Nilsen OG. Comparative pharmacokinetics of macrolides. J Antimicrob Chemother 1987; 20 Suppl. 20: 81–8PubMedCrossRefGoogle Scholar
  115. 115.
    Boccazzi A, Mezzopane A, Maffezzoli M, et al. Roxithromycin in paediatrics: pharmacokinetics and clinical efficacy of a single daily dose. 16th International Congress of Chemotherapy; 1989 Jun 11–16; Jerusalem, 220Google Scholar
  116. 116.
    Demotes-Mainard FM, Vincon GA, Albin HC. Pharmacokinetics of a new macrolide, roxithromycin, in infants and children. J Clin Pharmacol 1989; 29: 752–6PubMedGoogle Scholar
  117. 117.
    Roussel Uclaf. Roxithromycin prescribing information. Romainville, FranceGoogle Scholar
  118. 118.
    Höffler D, Koeppe P, Sörgel F, et al. The pharmacokinetics of roxithromycin in dialysis patients. 18th International Congress of Chemotherapy; 1993 Jun 27–Jul 2; Stockholm, 260Google Scholar
  119. 119.
    Babany G, Roulot D, Chrétien P, et al. Pharmacokinetics of single and repeated oral doses of roxithromycin in patients with cirrhosis [abstract]. 16th International Congress of Chemotherapy; 1989 Jun 11–16: Jerusalem: 222Google Scholar
  120. 120.
    Pechère J-C. Clinical evaluation of roxithromycin 300 mg once daily as an alternative to 150 mg twice daily. Diagn Microbiol Infect Dis 1992; 15 Suppl. 4: 111S–7SPubMedCrossRefGoogle Scholar
  121. 121.
    De Campora E, Camaioni A, Leonardi M. Comparative efficacy and safety of roxithromycin and clarithromycin in upper respiratory tract infections. Diagn Microbiol Infect Dis 1992; 15 Suppl. 4: 119S–22SPubMedCrossRefGoogle Scholar
  122. 122.
    Chow AW, Hall CB, Klein JO, et al. General guidelines for the evaluation of new anti-infective drugs for the treatment of respiratory tract infections. Clin Infect Dis 1992; 15 Suppl. 1: S62–88PubMedCrossRefGoogle Scholar
  123. 123.
    Fritz J, Fourie E, Pickard I, et al. A randomised controlled study of oral roxithromycin and amoxicillin plus clavulanic acid in the treatment of patient with acute maxillary sinusitis. 17th International Congress of Chemotherapy; 1991 Jun 23–28; BerlinGoogle Scholar
  124. 124.
    Higuera-Ramirez F, Hidalgo H. Multicentre study of the efficacy and tolerability of roxithromycin in the treatment of respiratory tract infections. Drug Invest 1991; 3 Suppl. 3: 38–46CrossRefGoogle Scholar
  125. 125.
    Manzini M, Caroggio A. Efficacy and tolerability of brodimoprim and roxithromycin in acute sinusitis of bacterial origin in adults. J Chemother 1993; 5: 521–5PubMedGoogle Scholar
  126. 126.
    Marsac JH. An international clinical trial on the efficacy and safety of roxithromycin in 40,000 patients with acute community-acquired respiratory tract infections. Diagn Microbiol Infect Dis 1992; 15 Suppl. 4: 81S–4SPubMedCrossRefGoogle Scholar
  127. 127.
    Saldarriaga A. Roxithromycin 150 mg bid in the treatment of sinusitis [abstract]. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  128. 128.
    Sanchez L. Roxithromycin in the treatment of pharyngotonsill-itis. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  129. 129.
    Peterslund NA, Hänninen P, Schreiner A, et al. Roxithromycin in the treatment of pneumonia. J Antimicrob Chemother 1989; 23: 737–41PubMedCrossRefGoogle Scholar
  130. 130.
    Saenghirunvattana S. Treatment of outpatients with community-acquired pneumonia with roxithromycin. J Med AssocThai 1992; 75: 283–6Google Scholar
  131. 131.
    Paulsen O, Christensson BA, Hebelka M, et al. Efficacy and tolerance of roxithromycin in comparison with erythromycin stéarate in patients with lower respiratory tract infections. Scand J Infect Dis 1992; 24: 219–25, No.2PubMedCrossRefGoogle Scholar
  132. 132.
    Scott WG, Tilyard MW, Dovey SM. Roxithromycin versus cefaclor in lower respiratory tract infection: a general practice pharmacoeconomic study. Pharmacoeconomics 1993; 4: 122–30PubMedCrossRefGoogle Scholar
  133. 133.
    Scott WG, Cooper BC, Scott HM, et al. Roxithromycin vs amoxycillin/clavulanic acid for community treated lower respiratory tract infection. A pharmacoeconomic study [abstract]. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  134. 134.
    Sliman NA. Roxithromycin in empiric five day treatment of respiratory tract infections [abstract no. 82]. 18th International Congress of Chemotherapy; 1993 Jun 27–Jul 2; Stockholm: 136Google Scholar
  135. 135.
    Dautzenberg B, Scheimberg A, Brambilla C, et al. Comparison of two oral antibiotics, roxithromycin and amoxicillin plus clavulanic acid, in lower respiratory tract infections. Diagn Microbiol Infect Dis 1992; 15 Suppl. 4: 85S–9SPubMedCrossRefGoogle Scholar
  136. 136.
    Tilyard MW, Dovey SM. A randomized double-blind controlled trial of roxithromycin and cefaclor in the treatment of acute lower respiratory tract infections in general practice. Diagn Microbiol Infect Dis 1992; 15 Suppl. 4: 97S–101SPubMedCrossRefGoogle Scholar
  137. 137.
    Laurent K. Efficacy, safety and toleration of azithromycin versus roxithromycin in the treatment of acute lower respiratory tract infections [abstract]. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  138. 138.
    Mühlbacher J, Ridl W, Sarffy-Panosch B, et al. Josamycin (J) in comparison to clari- (C) and roxithromycin (R) in the treatment of bronchitis [abstract no. 250]. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  139. 139.
    Champetie de Ribes D, Jockey C, Gaudouen G. A study of the effectiveness and tolerance of roxithromycin in lower respiratory tract infections. Sem Hop 1989; 65: 2819–21Google Scholar
  140. 140.
    De Vlieger A, Druart M, Puttemans M. Roxithromycin versus doxycycline in the treatment of acute exacerbations of chronic bronchitis. Diagn Microbiol Infect Dis 1992; 15 Suppl. 4: 123S–7SPubMedCrossRefGoogle Scholar
  141. 141.
    Poirier R. Comparative study of clarithromycin and roxithromycin in the treatment of community-acquired pneumonia. J Antimicrob Chemother 1991; 27 Suppl. A: 109–16PubMedCrossRefGoogle Scholar
  142. 142.
    Brambilla C. A multicentre study to evaluate the efficacy and safety of roxithromycin (once a day) vs erythromycin in the treatment of community-acquired pneumonia. 18th International Congress of Chemotherapy; 1993 Jun 27–Jul 2; Stockholm, 352Google Scholar
  143. 143.
    Soejima R, Niki Y, Hino J, et al. Double-blind comparative study of roxithromycin (RU 28965) and midecamycin acetate (MOM) in the treatment of pneumonia. Kansenshogaku Zasshi 1990; 63: 501–29Google Scholar
  144. 144.
    Stamboulian D, Perianu M. The efficacy of roxithromycin (300 mg once daily or 150 mg BID) in the treatment of “atypical” pneumonia in an international multicentre study. 17th International Congress of Chemotherapy; 1991 Jun 23–28; BerlinGoogle Scholar
  145. 145.
    Schönwald S, Car V, Kuzman I, et al. Comparison of Rulid (Roxithromycin) and erythromycin in the treatment of atypical pneumonias [abstract]. 16th International Congress of Chemotherapy; 1989 Jun 11–16, JerusalemGoogle Scholar
  146. 146.
    Cooper BC, Mullins PR, Jones MR, et al. Clinical efficacy of roxithromycin in the treatment of adults with upper and lower respiratory tract infections due to Haemophilus influenzae. Ameta-analysis of 12 clinical studies. Drug Invest 1994; 7: 229–314Google Scholar
  147. 147.
    Agache P, Amblard P, Moulin G, et al. Roxithromycin in skin and soft tissue infections. J Antimicrob Chemother 1987; 20 Suppl. B: 153–6PubMedCrossRefGoogle Scholar
  148. 148.
    Nohara N, Akagi M, Kanzaki H. Comparative double blind test of roxithromycin and josamycin on purulent diseases. Chemotherapy Tokyo 1989; 37: 1518–9Google Scholar
  149. 149.
    Bernard P, Plantin P, Roger H, et al. Roxithromycin versus penicillin in the treatment of erysipelas in adults: a comparative study. Br J Dermatol 1992; 127: 155–9PubMedCrossRefGoogle Scholar
  150. 150.
    Badile S, Bruno E, Porcellini A, et al. Roxithromycin in odontologie infections. 16th International Congress of Chemotherapy; 1989 Jun 11–16: Jerusalem, 222Google Scholar
  151. 151.
    Bercy P, Burguet J, Gossiaux T, et al. Treatment of dental infections: a double blind comparison of roxithromycin versus amoxycillin. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  152. 152.
    Deffez J-P, Scheimberg A, Rezvani Y. Multicenter double-blind study of the efficacy and tolerance of roxithromycin versuserythromycin ethylsuccinate in acute orodental infection in adults. Diagn Microbiol Infect Dis 1992; 15 Suppl. 4: 133S–7SPubMedCrossRefGoogle Scholar
  153. 153.
    Panattoni E, Marcucci M, Gabriele M, et al. Clinical efficacy of roxithromycin in patients affected by acute odontogenic infections. Minerva Stomatologica 1991; 40: 273–6PubMedGoogle Scholar
  154. 154.
    Sasaki J, Morihana T. Double-blind comparison of roxithromycin and josamycin in odontogenic infections [abstract]. 16th International Congress of Chemotherapy; 1989 Jun 11–16: Jerusalem, 223Google Scholar
  155. 155.
    Burquet J, Smets P, Wodelet J, et al. Double-blind study comparing efficacy and tolerance of roxithromycin and spiramycin in stomatology. 16th International Congress of Chemotherapy; 1989 Jun 11–16: Jerusalem, 223Google Scholar
  156. 156.
    Bajares de Lilue M, Mazzali de Ilja R, Santiago A, et al. Comparative study between roxithromycin and doxycycline in mycoplasma and chlamydial gynaecological infections. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  157. 157.
    Hoyme UB, Alimi M, Feldmann HU, et al. Roxithromycin v.s. doxycycline in treatment of cervicitis. 16th International Congress of Chemotherapy; 1989 Jun 11–16: Jerusalem, 226Google Scholar
  158. 158.
    Lidbrink P, Bygdeman S, Emtestam L, et al. Roxithromycin compared to doxycycline in the treatment of genital chlamyd ial infection and non-specific urethritis. Int J STD AIDS 1993; 4: 110–3PubMedGoogle Scholar
  159. 159.
    Narimatsu A, Ito T, Ono M, et al. Chlamydial infections in the fields of gynecology and obstetrics [abstract no.964]. 18th International Congress of Chemotherapy; 1993 Jun 27–Jul 2; Stockholm, 283Google Scholar
  160. 160.
    Negosanti N, d’Antuono A. Efficacy of roxithromycin vs minocycline in the treatment of non gonococcal urethritis: clinical and microbiological aspects. 16th International Congress of Chemotherapy; 1989 Jun 11–16; Jerusalem, 252Google Scholar
  161. 161.
    Rosales M, Dominguez V, Bonacho I. Roxitromycine versus doxycycline in the treatment of cervicitis due to Chlamydia trachomatis in asymptomatic women. Rev Clin Esp 1993; 192: 253–5PubMedGoogle Scholar
  162. 162.
    Siboulet A. Roxithromycin in non gonococcal cervico-vaginitis [abstract]. 16th International Congress of Chemotherapy; 1989 Jun 11–16: Jerusalem; 252Google Scholar
  163. 163.
    Van Schouwenburg J, De Bruyn O, Heyns A, et al. A randomised, comparative study of the efficacy and tolerance of roxithromycin and doxycycline in the treatment of women with positive endocervical cultures for Chlamydia trachomatis and Ureaplasma urealyticum in an in-vitro fertilization programme. 17th International Congress of Chemotherapy; 1991 Jun 23–28; BerlinGoogle Scholar
  164. 164.
    Bircher AJ, Geizer D, Rufli T. Roxithromycin in the treatment of non-gonococcal urethritis. A double blind comparison of two treatment regimens [abstract]. 16th International Congress of Chemotherapy; 1989 Jun 11–16; Jerusalem, 226Google Scholar
  165. 165.
    Durant J, Hazime F, Bernard E, et al. An open randomized study of roxithromycin (RO) efficacy and tolerance in the primary prevention (PP) of pneumocystosis (PC) and cererbal toxoplasmosis (CT) in 52 HIV-positive patients [abstract no.1216]. 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 1991 Oct 11–14; AnaheimGoogle Scholar
  166. 166.
    Labenz J, Borsch G. Evidence for the essential role of Helicobacter pylori in gastric ulcer disease. Gut 1994; 35: 19–22PubMedCrossRefGoogle Scholar
  167. 167.
    Bayerdörffer E, Mannes GA, Sommer A, et al. High dose omeprazole treatment combined with amoxicillin eradicates Helicobacter pylori. Eur J Gastroenterol Hepatol 1992; 4: 697–702Google Scholar
  168. 168.
    Labenz J, Gyenes E, Rühl GH, et al. Efficacy of omeprazole and amoxicillin to eradicate HP. Am J Gastroenterol 1992; 87: 1271Google Scholar
  169. 169.
    Logan RPH, Gummert PA, Hegarty BT, et al. Clarithromycin and omeprazole for helicobacter pylori. Lancet 1992; 340: 239PubMedCrossRefGoogle Scholar
  170. 170.
    Okamoto S, Haruma K, Kawaguchi H, et al. Study on eradication of helicobacter pylori by the combination use of roxithromycin, bismuth subnitrate, and omeprazole [abstract no. 960]. 18th International Congress on Chemotherapy; 1993 Jun 27–Jul 2; Stockholm; 1993, 282Google Scholar
  171. 171.
    Burette A, Glupcznski Y, Deprez C, et al. Lansoprazole plus roxithromycin and metronidazole for eradication of H. pylori results of a pilot study [abstract no. 319]. Second International Conference on the Macrolides, Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  172. 172.
    Bazet MC, Blanc F, Chumdermpadetsuk S, et al. Roxithromycin in the treatment of paediatric infections. Br J Clin Pract 1988; 42 Suppl. 55: 117–8Google Scholar
  173. 173.
    Casellas JM, Rodriguez HA, Fernandez-Macloughlin GJ, et al. Efficacy of roxithromycin in the treatment of acute otitis media in infants. Br J Clin Pract 1988; 42 Suppl. 55: 113–4Google Scholar
  174. 174.
    Stamboulian D, Fernandez-Macloughlin GJ, Lanoël JL, et al. Clinical evaluation of roxithromycin in 101 children. Br J Clin Pract 1988; 42 Suppl. 55: 115–6Google Scholar
  175. 175.
    Salvarezza C, Villar E, Ballario M. Estudio comparativo de la eficacia y tolerancia clinica de roxitromicina vs. amoxicilina en neumopatia extrahospitalarias en pediatria. Prensa Med Argent 1989; 76: 127–30Google Scholar
  176. 176.
    Laurencena E, Forti MJ. Roxithromycin in the treatment of acute otitis media in children. Prensa Med Argent 1992; 79: 577–9Google Scholar
  177. 177.
    Haentjes M, Levy J, De Boeck M, et al. Early treatment with roxithromycin of camphylobacter associated enteritis in children [abstract]. 16th International Congress of Chemotherapy; 1989 Jun 11–16, JerusalemGoogle Scholar
  178. 178.
    Blanc F, D’Enfant J, Fiessinger S, et al. An evaluation of tolerance of roxithromycin in adults. J Antimicrob Chemother 1987; 20 Suppl. B: 179–83PubMedCrossRefGoogle Scholar
  179. 179.
    Bégué P, Astruc J, Safran C, et al. The overall safety of oral roxithromycin in paediatric clinical studies [abstract]. Second International Conference on the Macrolides Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar
  180. 180.
    Dubois A, Nakache N, Raffanel C, et al. Hépatite aiguë cholestatique après prise de roxithromycine. Gastroenterol Clin Biol 1989; 13: 317–8PubMedGoogle Scholar
  181. 181.
    Delcourt A, Lambert M, Brenard R. Reversible liver injury possibly due to roxithromycin therapy. Acta Clin Belg 1990; 45: 206–7, No.3PubMedGoogle Scholar
  182. 182.
    Esteban A, Molina MJ, Soto C. Acute cholestatic hepatitis due to roxitromycine. Rev Clin Esp 1993; 192: 352–3PubMedGoogle Scholar
  183. 183.
    Pedersen FM, Bathum L, Fenger C. Acute hepatitis and roxithromycin. Lancet 1993; 341: 251–2PubMedCrossRefGoogle Scholar
  184. 184.
    Pillans P, Maling T. Roxithromycin and hepatitis. Drug Invest 1993; 6: 296–9CrossRefGoogle Scholar
  185. 185.
    Anonymous. Roxithromycine et hepatite [in French]. Folia Pharmaco Therapeutica 1990; 17: 21Google Scholar
  186. 186.
    Souweine B, Fialaip J, Aumaitre O, et al. Acute pancreatitis associated with roxithromycin therapy. DICP 1991; 25: 1137PubMedGoogle Scholar
  187. 187.
    Roujeau J-C, Bioulac-Sage P, Bourseau C, et al. Acute generalized exanthematous pustulosis. Arch Dermatol 1991; 127: 1333–8PubMedCrossRefGoogle Scholar
  188. 188.
    Wehrmann T, Rudolph U, Lembcke B, et al. Roxithromycin and erythromycin exert different effects on postprandial antroduodenal motor function and gastrointestinal symptoms inhealthy subjects. Eur J Gastroenterol Hepatol 1993; 5: 829–34Google Scholar
  189. 189.
    Pecquet S, Chachaty E, Tancrede C, et al. Effects of roxithromycin on fecal bacteria in human volunteers and resistance to colonization in gnotobiotic mice. Antimicrob Agents Chemother 1991; 35: 548–52PubMedCrossRefGoogle Scholar
  190. 190.
    Borderon JC, Borderon E, Laugier J, et al. Effect of roxithromycin on aerobic faecal flora in children, [in French]. Pathol Biol 1989; 37: 353–7PubMedGoogle Scholar
  191. 191.
    Delaforge M, Sartori E, Mansuy D. Effects of roxithromycin on rat hepatic P-450 cytochromes: comparison with troleandomycin and erythromycin. Br J Clin Pract 1988; 42 Suppl. 55: 67–9Google Scholar
  192. 192.
    Delaforge M, Satori E, Mansuy D. In vivo and in vitro effects of a new macrolide antibiotic roxithromycin on rat liver cycytochrome P450: comparison with troleandomycin and erythromycin. Chemical-Biological Interactions 1988; 68: 179–88CrossRefGoogle Scholar
  193. 193.
    Villa P, Sassella D, Corada M, et al. Toxic effects of erythromycin base, estolate and RU 28965, a new macrolide, on drugmetabolizing enzymes in rat liver [abstract]. 7th International Symposium on Future Trends in Chemotherapy; 1986 May 26–28; TirreniaGoogle Scholar
  194. 194.
    Saint-Salvi B, Tremblay D, Surjus A, et al. A study of the interaction of roxithromycin with theophylline and carbamaze-pine. J Antimicrob Chemother 1987; 20 Suppl. B: 121–9PubMedCrossRefGoogle Scholar
  195. 195.
    Bandera M, Fioretti M, Rimoldi R, et al. Roxithromycin and controlled release theophylline, an interaction study. Chemioterapia 1988; 7: 313–6PubMedGoogle Scholar
  196. 196.
    Periti P, Mazzei T, Mini E, et al. Pharmacokinetic drug interactions of macrolides. Clin Pharmacokinet 1992; 23: 106–31PubMedCrossRefGoogle Scholar
  197. 197.
    Hashiguchi K, Niki Y, Soejima R. Roxithromycin does not raise serum theophylline levels. Chest 1992; 102: 653–4PubMedCrossRefGoogle Scholar
  198. 198.
    Billaud EM, Guillemain R, Fortineau N, et al. Interaction between roxithromycin and cyclosporin in heart transplant patients. Clin Pharmacokinet 1990; 19: 499–502PubMedCrossRefGoogle Scholar
  199. 199.
    Meyer B, Muller F, Wessels P, et al. A model to detect interactions between roxithromycin and oral contraceptives. Clin Pharmacol Ther 1990; 47: 671–4PubMedCrossRefGoogle Scholar
  200. 200.
    Paulsen O, Nilsson L-G, Saint-Salvi B, et al. No effect of roxithromycin on pharmacokinetic or pharmacodynamic properties of warfarin or its enantiomers. Pharmacol Toxicol 1988; 63: 215–20PubMedCrossRefGoogle Scholar
  201. 201.
    Backman J, Aranko K, Himberg JJ, et al. Effect of roxithromycin on pharmacokinectics and pharmacodynamics of midazolam [abstract]. 16th International Congress of Chemotherapy; 1989 Jun 11–16: Jerusalem, 189Google Scholar
  202. 202.
    Nilsen. Plasma pharmacokinetics of macrolides with reference to total and free concentrations. Second International Conference on the Macrolides, Azalides and Streptogramins; 1994 Jan 19–22; VeniceGoogle Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Anthony Markham
    • 1
  • Diana Faulds
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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