PHARMACOKINETICS OF BACAMPICILLIN IN EQUIDS

Bacampicillin hydrochloride is an ester prodrug that is hydrolyzed to ampicillin after its absorption from the gastrointestinal tract. It wa s administered intragastrically at a dose rate of 13.5 mg/kg of body w eight to ponies and horses, and was highly bioavailable (F = 41.0%), c ompared with other penicillins in adult horses. The high peak ampicill in plasma concentration of 6.1 +/- 0.5 mu g/ml achieved and persistenc e of the antibiotic at concentration of 0.3 +/- 0.1 mu g/ml 6 hours af ter its intragastric administration, suggest that bacampicillin hydroc hloride may reach suitable bactericidal concentrations for treatment o f infections caused by susceptible microorganisms. In a separate exper iment, dichlorvos, an organophosphate compound that inhibits some of t he esterase activity in plasma, was administered orally to the same an imals at a dose rate of 40 mg/kg, followed by intragastric administrat ion of bacampicillin hydrochloride at a dose of 13.5 mg/kg. Plasma pse udocholinesterase and erythrocyte acetylcholinesterase activities were reduced to < 5% of reference (predichlorvos) values after dichlorvos administration. However, rate of hydrolysis of bacampicillin into ampi cillin was not affected. Consequently, the disposition and fate of bac ampicillin when administered intragastrically 1 day after dichlorvos a dministration were similar to the values obtained after administration of bacampicillin alone. Intragastric coadministration of probenecid a t a dose rate of 75 mg/kg and bacampicillin at 13.5 mg/kg limited abso rption of the antibiotic from the gastrointestinal tract. This suggest s existence of a common transport mechanism for bacampicillin and prob enecid in the gastrointestinal wall, and precludes use of this combina tion for treatment. The bioavailable fraction of ampicillin after comb ination treatment indicated prolonged residence time in the plasma, pr esumably as a consequence of reduced renal tubular secretion.