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Chronopharmacokinetics of metronidazole in healthy human volunteers


Jacob A Kolawole
Innocent U Ameh

Abstract

Metronidazole is a synthetic antimicrobial agent widely used in different clinical conditions. Changes in pharmacokinetic profile of drugs caused by differences in dosing time has been known to have led to toxicities, treatment failures and in some cases more beneficial effects, depending on the parameters affected. This study was designed to investigate the circadian changes in the pharmacokinetics of metronidazole at three different dosing times; 0700 h, 1300 h, and 1900 h. Six healthy male volunteers, age 26.50 ± 2.66 years, weighing 58.33± 5.61 kg took part in the study. They were administered with 400mg oral metronidazole at the three circadian times, after a fasting period of not less than 4 h for each phase of the study. Saliva samples [2mL] were collected at 0, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, and 12.0 h. Spectrophotometric method was used to determine the metronidazole concentration in saliva, and the pharmacokinetic parameters (Ka, t1/2a, Cmax, Tmax, AUC, Ke and t1/2e) calculated. The values obtained, though varied, were found to be in similar ranges with previously reported values. There were significant differences in Ka and t1/2a values (P<0.05) with respect to the time of administration while the other parameters were not significantly altered.

Key Words: Chronopharmacokinetics; metronidazole; human volunteers

Journal of Pharmacy and Bioresources Vol.1(1) 2004: 29-34

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