Summary
Concentrations of metronidazole and tinidazole in serum and gynecological organs were analyzed after a single 500 mg intravenous infusion and after three days of treatment with 400 mg t.i.d. of metronidazole or 500 mg b.i.d. of tinidazole. The studies were performed in 67 patients subjected to hysterectomy and/or oophorectomy because of myomatosis uteri, carcinoma uteri or endometriosis. At the time of organ removal (about 30 min after infusion), metronidazole and tinidazole levels in serum were 14.5 ± 0.45 mg/l and 12.3 ± 0.38 mg/l, respectively. Concentrations of both drugs in the uterus and Fallopian tube were about the same as the simultaneous serum levels and concentrations in the ovaries about 55% thereof. At steady-state, the concentrations of tinidazole in serum (23.5 ± 1.0 mg/l) were remarkably higher than those of metronidazole (13.5 ± 0.84 mg/l) about three hours after the last oral dose. Drug concentrations in organs of the female reproductive tract were 70 to 100% those of the simultaneous serum levels.
Zusammenfassung
Die Konzentrationen von Metronidazol und Tinidazol in Serum und Genitalorganen wurden nach einer intravenösen Einzelinfusion von 500 mg sowie nach dreitägiger oraler Behandlung mit 400 mg Metronidazol dreimal täglich oder 500 mg Tinidazol, zweimal täglich, bestimmt. Die Untersuchungen wurden bei 67 Patientinnen durchgeführt, bei denen eine Hysterektomie und/oder Oophorektomie wegen Myomatosis uteri, Uteruskarzinom oder Endometriose vorgenommen wurde. Zum Zeitpunkt der Organentnahme (etwa 30 min nach Infusion) betrugen die Metronidazol-und Tinidazolspiegel im Serum 14,5 ± 0,45 mg/l bzw. 12,3 ± 0,38 mg/l. Die Konzentrationen der beiden Medikamente im Uterus und in der Tube entsprachen den gleichzeitig bestimmten Serumspiegeln; die Konzentrationen in den Ovarien lagen bei etwa 55% der Serumspiegel. Im Steady state, etwa drei Stunden nach der letzten oralen Dosis, waren die Serumkonzentrationen von Tinidazol mit 23,5 ± 1,0 mg/l erheblich höher als die Metronidazolserumspiegel (13,5 ± 0,84 mg/l). Die Konzentrationen der Medikamente in den weiblichen Genitalorganen lagen bei 70 bis 100% der simultanen Serumspiegel.
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Literature
Jokipii, A. M. M., Myllylä, V. V., Hokkanen, E., Jokipii, L. Penetration of the blood brain barrier by metronidazole and tinidazole. J. Antimicrob. Chemother. 3 (1977) 239–245.
Carmine, A. A., Brogden, R. N., Heel, R. C., Speight, T. M., Avery, G. S. Tinidazole in anaerobic infections. A review of its antibacterial activity, pharmacological properties and therapeutic efficacy. Drugs 24 (1982) 85–117.
Wood, B. A., Faulkner, J. K., Monro, A. M. The pharmacokinetics, metabolism and tissue distribution of tinidazole. J. Antimicrob. Chemother. 10 (1982) 43–57.
Ripa, T., Weström, L., Mårdh, P.-A., Andersson, K.-E. Concentrations of tinidazole in body fluids and tissues in gynaecological patients. Chemotherapy 23 (1977) 227–235.
Viitanen, J., Auvinen, O., Tunturi, T. Serum and tissue tinidazole concentrations after intravenous infusion. Chemotherapy 29 (1983) 13–17.
Hunt, P. S., Davidson, A. J. L., Alden, J., Cheng, S. Bile and serum levels of tinidazole after a single oral dose. Br. J. Clin. Pharmacol. 13 (1982) 233–234.
Welling, P. G., Monro, A. M. The pharmacokinetics of metronidazole and tinidazole in man. Arzneimittelforsch. 22 (1972) 2128–2132.
Mattila, J., Männistö, P. T., Mäntylä, R., Nykänen, S., Lamminsivu, U. Pharmacokinetic comparison of metronidazole and tinidazole upon different routes of administration. Antimicrob. Agents Chemother. 23 (1983) 721–725.
Marques, R. A., Stafford B., Flynn, N., Sodée, W. Determination of metronidazole and misonidazole and their metabolites in plasma and urine by high-performance liquid chromatography. J. Chromatogr. 146 (1978) 163–166.
Knoben, J. E., Anderson, P. O., Watanabe, A. S. Handbook of clinical drug data. 4th ed. Drug Intelligence Publications, Hamilton 1980, p. 12.
Brogden, R. N., Heel, R. C., Speight, T. M., Avery, G. S. Metronidazole in anaerobic infections: a review of its activity, pharmacokinetics and therapeutic use. Drugs 16 (1978) 387–417.
Charuel, C., Nachbaur, J., Monro, A. M., de Palol, J. The pharmacokinetics of intravenous tinidazole in man. J. Antimicrob. Chemother. 8 (1981) 343–346.
Cocks, P. S., Munro, R., Norton, B., Nutting, J., Shanker, S., Cheng, S. Prospective comparative trial of tinidazole and metronidazole as prophylaxis for elective hysterectomy. Aust. NZ J. Obstet. Gynecol. 21 (1981) 116–120.
Mattila, J., Nerdrum, K., Rouhiainen, H., Männistö, P. T., Tuovinen, E., Lamminsivu, U. Penetration of metronidazole and tinidazole into the aqueous humor in man. Chemotherapy 29 (1983) 188–191.
von Konow, L., Nord, C. E. Concentrations of tinidazole and metronidazole in serum, saliva and alveolar bone. J. Antimicrob. Chemother. 10 Suppl. A (1982) 165–172.
Lundberg, C., Lönnroth, J., Marklund, G., Nord, C. E. Tinidazole in the treatment of infections of the upper respiratory tract. Scand. J. Infect. Dis. 26 Suppl. (1981) 130–134.
Bystedt, H., von Konow, L., Nord, C. E. Effect of tinidazole on postoperative complications after surgical removal of impacted mandibular third molars. Scand. J. Infect. Dis. 26 Suppl. (1981) 135–139.
Männistö, P. T., Karhunen, M., Koskela, O., Suikkari, A.-M., Mattila, J., Haataja, H. Concentrations of tinidazole in breast milk. Acta Pharmacol. Toxicol. 53 (1983) 254–256.
Georg, R. H., Bint, A. J. Treatment of a brain abscess due toBacteroides fragilis with metronidazole. J. Antimicrob. Chemother. 2 (1976) 101–105.
Ingman, H. R., Selkon, J. B., Roxby, C. M. Bacteriological study of otogenic cerebral abscesses; chemotherapeutic role of metronidazole. Br. Med. J. 2 (1977) 991–993.
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Männistö, P., Haataja, H., Karhunen, M. et al. Concentrations of metronidazole and tinidazole in female reproductive organs after a single intravenous infusion and after repeated oral administration. Infection 12, 197–201 (1984). https://doi.org/10.1007/BF01640899
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DOI: https://doi.org/10.1007/BF01640899