Disposition and oral bioavailability of amoxicillin and clavulanic acid in pigs
The pharmacokinetic properties of amoxicillin and clavulanic acid were studied in healthy, fasted pigs after single intravenous (i.v.) and oral (p.o.) dosage of 20 mg/kg of amoxicillin and 5 mg/kg of clavulanic acid. The plasma concentrations of the drugs were determined by validated high-performance liquid chromatographic methods and the pharmacokinetic parameters were calculated by compartmental and noncompartmental analyses. After i.v. administration of the two drugs, plasma concentration-time curves were best described by a three-compartmental open model for amoxicillin and a two-compartmental open model for clavulanic acid. Amoxicillin (with a t(1/2 gamma) = 1.03 h and a clearance of 0.58 L/h.kg) and clavulanic acid (with a t(1/2 beta) of 0.74 h and a clearance of 0.41 L/h.kg) were both rapidly eliminated from plasma. Both drugs had apparently the same volume of distribution of 0.34 L/kg. After p.o. administration of the two drugs, a noncompartmental model was used. Elimination half-lives of amoxicillin and clavulanic acid were not significantly different, i.e. 0.73 and 0.67 h respectively. The mean maximal plasma concentrations of amoxicillin and clavulanic acid were 3.14 and 2.42 mg/L, and these were reached after 1.19 and 0.88 h respectively. The mean p.o. bioavailability was found to be 22.8% for amoxicillin and 44.7% for clavulanic acid.
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