Pharmaceutisch Weekblad

, Volume 9, Issue 2, pp 110–116 | Cite as

Pharmacokinetics of cefradine, sulfamethoxazole and trimethoprim and their metabolites in a patient with peritonitis undergoing continuous ambulatory peritoneal dialysis

  • M. Martea
  • Y. A. Hekster
  • T. B. Vree
  • A. J. Voets
  • J. H. M. Berden
Pharmacokinetics and Organ Dysfunction


Cefradine and co-trimoxazole pharmacokinetics were studied in a patient with peritonitis that complicated continuous ambulatory peritoneal dialysis (CAPD). Concentrations in the plasma reached after oral administration of 500 mg cefradine four times daily and 400/80 mg co-trimoxazole four times daily were for cefradine 100μg/ml, for trimethoprim 15μg/ml, and for sulfamethoxazole 100μ/ml, respectively. In the dialysate concentrations were reached of 35–70μ/ml cefradine, 2–5μ/ml trimethoprim and 8–17μg/ml sulfamethoxazole. The values for sulfamethoxazole are regarded too low to be clinically effective. Half-lives protein binding values and CAPD clearances are presented. Low CAPD clearances were obtained during the night and high values during the day. The dosage yielded too high plasma trimethoprim concentrations, while sulfamethoxazole dialysate concentrations were too low. It seems questionable therefore whether co-trimoxazole can be used orally for the treatment of CAPD peritonitis.

Key words

Cefradine Clearance Kidney diseases Metabolism Peritoneal dialysis, continuous ambulatory Pharmacokinetics Protein binding Sulfamethoxazole Trimethoprim 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Levey A, Harrington J. Continuous peritoneal dialysis for chronic renal failure. Medicine 1982;61:330–9.Google Scholar
  2. 2.
    Golper T, Bennett W, Jones S. Peritonitis associated with chronic peritoneal dialysis. Dial Transplant 1978; 7:1173–8.Google Scholar
  3. 3.
    Rubin J, Rogers W, Taylor H, et al. Peritonitis during continuous ambulatory peritoneal dialysis. Ann Intern Med 1980;92:7–13.Google Scholar
  4. 4.
    Danziger LH. Controversies in antimicrobial therapy: innovative methods of administration. Am J Hosp Pharm 1986;43:646–52.Google Scholar
  5. 5.
    Knight KR, Polak A, Crump J, et al. Laboratory diagnosis and oral treatment of CAPD peritonitis. Lancet 1982;2:1301–4.Google Scholar
  6. 6.
    Boeschoten EW, Rietra PJ, Krediet RT, et al. CAPD peritonitis: a prospective randomized trial of oral versus intraperitoneal treatment with cephradine. J Antimicrob Chemother 1985;16:789–97.Google Scholar
  7. 7.
    Drew PJT, Casewell MW, Desai N, et al. Cephalexin for the oral treatment of CAPD peritonitis. J Antimicrob Chemother 1984;13:153–9.Google Scholar
  8. 8.
    Searle M, Raman GV. Oral treatment of peritonitis complicating continuous ambulatory peritoneal dialysis. Clin Nephrol 1985;23:241–4.Google Scholar
  9. 9.
    Glasson P, Favre H. Treatment of peritonitis in continuous peritoneal dialysis patients with co-trimoxazole. Nephron 1984;36:65–7.Google Scholar
  10. 10.
    Singlas E, Rottembourg J, De Martin A, et al. Pharmacokinetics of co-trimoxazole using the peritoneal route: consequence for the treatment of peritonitis in patients maintained on peritoneal dialysis. In: Moncrief JW, Topovich RP, eds. CAPD update. New York: Masson, 1981:63–6.Google Scholar
  11. 11.
    Singlas E, Colin JN, Rottembourg J, et al. Pharmacokinetics of sulfamethoxazole-trimethoprim combination during chronic peritoneal dialysis: effects of peritonitis. Eur J Clin Pharmacol 1982;21:409–15.Google Scholar
  12. 12.
    Halstenson CE, Blevins RB, Salem NG, Matzje GR. Trimethoprim-sulfamethoxazole pharmacokinetics during continuous ambulatory peritoneal dialysis. Clin Nephrol 1984;22:239–43.Google Scholar
  13. 13.
    Bratton AC, Marshall EK. New coupling component for sulfanilamide determination. J Biol Chem 1939; 128:537–50.Google Scholar
  14. 14.
    Vree TB, Hekster YA, Tijhuis MW. Metabolism of sulfonamides. Antibiot Chemother 1985;34:5–65.Google Scholar
  15. 15.
    Vree TB, Hekster YA, Damsma JE, Van der Kleijn E, O'Reilly WJ. Pharmacokinetics of N1-acetyl- and N4- acetylsulfamethoxazole in man. Clin Pharmacokinet 1979;4:310–9.Google Scholar
  16. 16.
    Clarke GS, Robinson ML. HPLC analysis of Cephradine in human serum and urine. J Clin Hosp Pharm 1983;8:373–4.Google Scholar
  17. 17.
    Janknegt R, Koks CHW. Pharmacokinetic aspects during continuous ambulatory peritoneal dialysis: a literature review. Pharm Weekbl [Sci] 1984;6:229–36.Google Scholar
  18. 18.
    Johnson CA, Welling PG, Zimmerman SW. Pharmacokinetics of oral cephradine in continuous ambulatory peritoneal dialysis patients. Nephron 1984;38:57–61.Google Scholar
  19. 19.
    Vree TB, Hekster YA, Van Dalen R. Some consequences of drug choice and dosage regimen for patients with impaired kidney function. Drug Intell Clin Pharm 1983;17:267–73.Google Scholar
  20. 20.
    Vree TB, Hekster YA. Renal excretion of sulfonamides. Antibiot Chemother 1985;34:66–120.Google Scholar
  21. 21.
    Nouws JFM, Vree TB, Hekster YA.In vitro antimicrobial activity of hydroxy and N4-acetyl sulfonamide metabolites. Vet Quart 1985;7:70–2.Google Scholar
  22. 22.
    Van Dalen R, Vree TB, Baars AM, Termond EFS. Dosage adjustment for ceftazidime in patients with impaired kidney function. Eur J Clin Pharmacol 1986;30:597–605.Google Scholar
  23. 23.
    Hekster YA, Vree TB, Van Dalen R, Van der Kleijn E, Hafkenscheid J. Pharmacokinetics of cefuroxime and cefoxitin with normal, impaired and probenecid functionally impaired kidney function. In: Nelson JD, Grassi C, eds. Current Chemotherapy and Infectious Disease. Washington: American Society for Microbiology. 1980:570–3.Google Scholar
  24. 24.
    Vree TB, Martea M, Hekster YA, et al. Deterioration of human kidney function by high doses of co-trimoxazole in man. Pharm Weekbl [Sci] 1987:9:117–24.Google Scholar
  25. 25.
    Vree TB, Hekster YA, Hafkenscheid JCM, Van Dalen R, Friesen WT. The influence of the urine flow on renal clearance of creatinine in patients with normal and impaired kidney function. Drug Intell Clin Pharm 1981;15:194–8.Google Scholar
  26. 26.
    Hekster YA, Vree TB, Weemaes CMR, Rotteveel JJ. Toxicologic and pharmacokinetic evaluation of a case of vancomycin intoxication during continuous ambulatory peritoneal dialysis. Pharm Weekbl [Sci] 1986;8:293–7.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1987

Authors and Affiliations

  • M. Martea
    • 1
  • Y. A. Hekster
    • 1
  • T. B. Vree
    • 1
  • A. J. Voets
    • 2
  • J. H. M. Berden
    • 2
  1. 1.Department of Clinical PharmacySt. Radboud HospitalHB NijmegenThe Netherlands
  2. 2.Department of NephrologySt. Radboud HospitalHB NijmegenThe Netherlands

Personalised recommendations