Bioavailability and pharmacokinetics of metronidazole in fed and fasted horses |
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| Authors: | M Britzi M Gross E Lavy S Soback A Steinman |
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| Institution: | 1. National Residue Control Laboratory, Ministry of Agriculture, Kimron Veterinary Institute, Beit Dagan, Israel;2. Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel |
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| Abstract: | Britzi, M., Gross, M., Lavy, E., Soback, S., Steinman, A. Bioavailability and pharmacokinetics of metronidazole in fed and fasted horses. J. vet. Pharmacol. Therap. 33 , 511–514. Metronidazole (1‐2‐hydroxyethyl]‐2‐methyl‐5‐nitroimidazole) is a bactericidal antimicrobial agent used for treatment of infectious diseases caused by anaerobic bacteria and protozoa. Pharmacokinetics of metronidazole following its administration to horses was previously described ( Sweeney et al., 1986 ; Baggot et al., 1988 ; Specht et al., 1992 ; Steinman et al., 2000 ). The bioavailability (F) was 85% (ranging from 57% to 105%) and the time to reach maximum serum concentration (tmax) was 1–2 h after oral dose at 25 mg/kg body weight ( Sweeney et al., 1986 ). Baggot et al. (1988) found that F was 74.5% (ranging from 58.4% to 91.5%) and tmax was 1.5 h after oral dose at 20 mg/kg body weight. Specht et al. (1992) reported that F was 97% (ranging from 79% to 111%) and tmax was 40 min after oral dose at 15 mg/kg body weight. In an earlier study by our group F was 74% and tmax was 65 min after oral dose at 20 mg/kg body weight ( Steinman et al., 2000 ). These individual variations in F might be partially explained by the effect of feed, among other factors, mainly on metronidazole absorption. Interactions between food and drugs may reduce or increase the drug effect. The majority of clinically relevant food–drug interactions are caused by food‐induced changes on the bioavailability of the drug ( Schmidt & Dalhoff, 2002 ). In dogs, absorption of metronidazole is enhanced when given with food, but delayed in humans ( Plumb, 1995 ). Although, metronidazole is used commonly to treat various clinical conditions in horses with relatively little adverse effects ( Sweeney et al., 1991 ), narrow margin of safety was suggested because histological evidence of peripheral neurotoxicity and hepatotoxicity were noted in horses treated with doses as low as 30 mg/kg body weight every 12 h orally for 30 days ( White et al., 1996 ). For drugs with a narrow therapeutic index, even small changes in dose–response effects can have significant consequences ( Schmidt & Dalhoff, 2002 ). |
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