Pharmacokinetics of bacampicillin in equids

Patxi Sarasola From the Department of Veterinary Pharmacology, University of Glasgow Veterinary School, Bearsden Rd, Bearsden, Glasgow G61 1QH, Scotland, United Kingdom.

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 DVM, PhD
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Quintin A. McKellar From the Department of Veterinary Pharmacology, University of Glasgow Veterinary School, Bearsden Rd, Bearsden, Glasgow G61 1QH, Scotland, United Kingdom.

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 BVMS, PhD

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SUMMARY

Bacampicillin hydrochloride is an ester prodrug that is hydrolyzed to ampicillin after its absorption from the gastrointestinal tract. It was administered intragastrically at a dose rate of 13.5 mg/kg of body weight to ponies and horses, and was highly bioavailable (F = 41.0%), compared with other penicillins in adult horses. The high peak ampicillin plasma concentration of 6,1 ± 0,5 µg/ml achieved and persistence of the antibiotic at concentration of 0.3 ± 0.1 µg/ml 6 hours after its intragastric administration, suggest that bacampicillin hydrochloride may reach suitable bactericidal concentrations for treatment of infections caused by susceptible microorganisms.

In a separate experiment, dichlorvos, an organo-phosphate compound that inhibits some of the esterase activity in plasma, was administered orally to the same animals at a dose rate of 40 mg/kg, followed by intragastric administration of bacampicillin hydrochloride at a dose of 13.5 mg/kg. Plasma pseudocholines-terase and erythrocyte acetylcholinesterase activities were reduced to < 5% of reference (predichlorvos) values after dichlorvos administration. However, rate of hydrolysis of bacampicillin into ampicillin was not affected. Consequently, the disposition and fate of bacampicillin when administered intragastrically 1 day after dichlorvos administration were similar to the values obtained after administration of bacampicillin alone.

Intragastric coadministration of probenecid at a dose rate of 75 mg/kg and bacampicillin at 13.5 mg/ kg limited absorption of the antibiotic from the gastrointestinal tract. This suggests existence of a common transport mechanism for bacampicillin and probenecid in the gastrointestinal wall, and precludes use of this combination for treatment. The bioavailable fraction of ampicillin after combination treatment indicated prolonged residence time in the plasma, presumably as a consequence of reduced renal tubular secretion.

SUMMARY

Bacampicillin hydrochloride is an ester prodrug that is hydrolyzed to ampicillin after its absorption from the gastrointestinal tract. It was administered intragastrically at a dose rate of 13.5 mg/kg of body weight to ponies and horses, and was highly bioavailable (F = 41.0%), compared with other penicillins in adult horses. The high peak ampicillin plasma concentration of 6,1 ± 0,5 µg/ml achieved and persistence of the antibiotic at concentration of 0.3 ± 0.1 µg/ml 6 hours after its intragastric administration, suggest that bacampicillin hydrochloride may reach suitable bactericidal concentrations for treatment of infections caused by susceptible microorganisms.

In a separate experiment, dichlorvos, an organo-phosphate compound that inhibits some of the esterase activity in plasma, was administered orally to the same animals at a dose rate of 40 mg/kg, followed by intragastric administration of bacampicillin hydrochloride at a dose of 13.5 mg/kg. Plasma pseudocholines-terase and erythrocyte acetylcholinesterase activities were reduced to < 5% of reference (predichlorvos) values after dichlorvos administration. However, rate of hydrolysis of bacampicillin into ampicillin was not affected. Consequently, the disposition and fate of bacampicillin when administered intragastrically 1 day after dichlorvos administration were similar to the values obtained after administration of bacampicillin alone.

Intragastric coadministration of probenecid at a dose rate of 75 mg/kg and bacampicillin at 13.5 mg/ kg limited absorption of the antibiotic from the gastrointestinal tract. This suggests existence of a common transport mechanism for bacampicillin and probenecid in the gastrointestinal wall, and precludes use of this combination for treatment. The bioavailable fraction of ampicillin after combination treatment indicated prolonged residence time in the plasma, presumably as a consequence of reduced renal tubular secretion.

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