Pharmacokinetics of metronidazole in horses after intravenous, rectal and oral administration

Abstract

Metronidazole pharmacokinetics in horses was studied after intravenous (i.v.), rectal (p.r.) and oral (p.o.) administration at 20 mg/kg using a triple crossover study design. Metronidazole mean+/-SD half-life was 196+/-39, 212+/-30 and 240+/-65 min after i.v., p.r. and p.o. administration, respectively. The metronidazole clearance was 2.8 (mL/min/kg) and the volume of distribution at steady state was 0.68 L/kg. The pharmacokinetic parameters calculated for metronidazole after administration of the drug by the various routes showed that bioavailability (74+/-18 vs. 30+/-9%) and maximum serum concentration (22+/-8 vs. 9+/-2 microg /mL) were significantly higher after p.o. administration compared with p.r. administration. There were no significant differences in mean absorption time (45+/-69 vs. 66+/-18 min) and the time to reach maximum serum concentration (65+/-36 vs. 58+/-18 min). The results indicated that p.r. administration of metronidazole to horses, although inferior to p.o. administration in terms of bioavailability, provides an alternative route of administration when p.o. administration cannot be used.

Mucosal permeability of water‐soluble drugs in the equine jejunum: a preliminary investigation

“…The oral bioavailability for each drug was collected from the literature (Sweeney et al. , 1986; Steinman et al. , 2000; Latimer et al.…”

Pharmacokinetics of metronidazole in foals: influence of age within the neonatal period

“…It is likely that clearance rate increased further as the foals aged. This is further supported by the higher clearance rate previously reported for adult horses (2.8–6.7 mL/min/kg;Specht et al ., ; Steinman et al ., ). As metronidazole is primarily liver metabolized, this likely represents maturation of hepatic function.…”

“…The approximated intragastric bioavailability (F) was 100% for foals at 1–2.5 days of age. This is also similar to the IG bioavailability previously reported for adult horses (74–100%) (Specht et al ., ; Steinman et al ., ; Britzi et al ., ).…”

Effects of intrarectally administered omeprazole paste on gastric fluid pH in healthy adult horses

“…Differing rates of omeprazole absorption through the rectal mucosa, the large intestine's relatively smaller surface area per unit length available for drug absorption (compared with the small intestine), and the small amount of drug dispensed into the rectum (approximately 5 ml omeprazole paste per horse) could have accounted for the lower serum omeprazole concentrations and AUC reported in the present study. Drug inactivation or binding by faecal material have been suggested as potential causes for reduced bioavailability in studies examining the pharmacokinetics of rectally administered metronidazole (Steinman and others 2000) and cisapride (Steel and others 1999), and these factors may have been true in the present study as well. All horses defecated within the first two hours following the final intrarectal omeprazole administration, and there was macroscopic binding of omeprazole paste evident on the faeces, indicating that the amount of time that the drug actually spent in contact with the rectal mucosa was relatively short.…”