Pharmacokinetics of phenoxymethyl penicillin (penicillin V) in calves

Abstract

Phenoxymethyl penicillin (penicillin V) was administered intravenously (i.v.) and orally to pre-ruminant calves and the distribution and elimination kinetics, as well as the oral bioavailability, were determined. After i.v. injection, the drug was distributed rapidly in the body, the elimination half-life (t1/2 beta) was 34 min and the apparent volume of distribution at steady-state (Vd ss) was 0.30 l/kg. Mean peak serum drug concentrations were directly related to the oral dose administered, i.e. 0.22 microgram/ml, 1.06 micrograms/ml and 2.14 micrograms/ml after dosing at 10, 20 and 40 mg/kg, respectively. The elimination t1/2 of the drug after oral dosing varied between 90 and 110 min, and the oral bioavailability was approximately 30% of the dose. The co-administration of phenoxymethyl penicillin and probenecid resulted in elevation and prolongation of serum drug concentration. The percentage of drug bound to serum proteins was 78.8% +/- 8.2%. Phenoxymethyl penicillin was probably inactivated and degraded in the gastrointestinal tract of 6-week-old calves fed exclusively hay, silage and concentrates as very low and erratic serum drug concentrations were measured after these calves were dosed orally with the drug at 40 mg/kg. In view of the narrow antibacterial spectrum of the drug and the relatively high dose required, it appears that phenoxymethyl penicillin can only be of limited practical value for the treatment of bacterial infections in preruminant calves.

Bioavailability and disposition of sodium and procaine penicillin G (benzylpenicillin) administered orally with milk to calves

“…administration, which was consistent with earlier studies on ampicillin and amoxicillin (Ziv et al ., 1977). Examining data from a study which administered penicillin V, 10 mg/kg, orally to 2–3‐week‐old calves, the half‐lives of absorption and elimination were also similar (Soback et al ., 1987).…”

“…The other kinetic parameters of sodium penicillin G were similar to cattle following i.v. administration (Soback et al ., 1987; Volner et al ., 1987; Bengtsson et al ., 1997) and displayed the typical characteristics of the penicillin family of antibiotics. These characteristics include a rapid distribution phase, short half‐life of elimination, and Vd SS indicative of distribution to the vascular and the extracellular fluid (Riviere et al ., 1991).…”

“…When penicillin V was administered orally to 6‐week‐old weaned calves, the drug had very low absorption and minimal bioavailability (Soback et al ., 1987). As penicillin V resists hydrolysis in an acidic environment, the authors attributed the destruction to inactivation and degradation in the gastrointestinal tract of the calves.…”

“…The sampling times for the p.o. trials were chosen with the knowledge that peak plasma concentrations for similar β ‐lactam antibiotics occurred approximately 1.5–3 h after administration (Ziv et al ., 1977; Thompson & Black, 1978; Palmer et al ., 1983; Soback et al ., 1987).…”

“…Despite the use of penicillin G for many decades to treat lactating cows and the feeding of the withheld milk to calves, no definitive studies could be found on the bioavailability or disposition of penicillin G in the calf after ingestion of milk containing subtherapeutic concentrations of penicillin G. Research has been published on the bioavailability of other β ‐lactams in the calf (Larkin, 1972; Palmer et al ., 1977; Ziv et al ., 1977; Ziv & Horsey, 1979; Palmer et al ., 1983; Soback et al ., 1987), but not penicillin G. Penicillin G is degraded in the stomach by gastric acid resulting in limited absorption, however, the reported percentage of the dose absorbed (bioavailability) is quite varied (Huber, 1982; Knifton, 1982; Riviere et al ., 1991; Nathwani & Wood, 1993; Rang et al ., 1995; Mandell & William, 1996). The possibility of penicillin G causing drug residues when calves are fed waste milk has been suggested (Kesler, 1981).…”