The effect of phenylbutazone on the plasma disposition of penicillin G in the horse

Abstract

A pilot study in two ponies showed that the plasma concentrations of intramuscularly administered procaine penicillin were higher if phenylbutazone was administered concurrently. In two other trials, each involving five horses, intravenous sodium penicillin was administered with and without concurrent intravenously injected phenylbutazone, and procaine penicillin was injected intramuscularly with and without oral phenylbutazone. In both cases the plasma concentrations of penicillin were higher when phenylbutazone was given. The pharmacokinetic parameters indicated that the effect was probably due to a lower peripheral distribution because the penetration of penicillin into the tissues was greatly reduced.

An integrated experimental and physiologically based pharmacokinetic modeling study of penicillin G in heavy sows

“…The urine clearance rate constant also has impacts on the model predictions. The urinary clearance rate of heavy sows (0.8 L h ‐1 kg ‐1 ) is comparable (within twofold difference) with the reported clearance rates in sheep (0.55 L h ‐1 kg ‐1 ) and horses (0.51 L h ‐1 kg ‐1 ) (Firth, Nouws, Klein, & Driessens, ; Oukessou, Hossaini, Zine‐Filali, & Toutain, ; USP, ), but it is lower than the urinary clearance rate of 1.4 L h ‐1 kg ‐1 for market‐age swine (Li et al, ). The ~ twofold difference in urinary clearance between heavy sows and market‐age swine may contribute to the predicted longer withdrawal interval for penicillin G in the former than in the latter.…”

“…Overall the liver, kidney, and muscle partition coefficients in heavy sows were comparable to the experimental values from a previous PBPK model in rats (Tsuji et al, 1983) and the values in our previous PBPK model in market-age swine . However, additional studies that determine the values of partition coefficients in different tissues of swine using experimental methods (Pacifici & Viani, 1992;Tremblay, Kim, & Fisher, 2012) (Firth, Nouws, Klein, & Driessens, 1990;Oukessou, Hossaini, Zine-Filali, & Toutain, 1990;USP, 2007), but it is lower than the urinary clearance rate of 1.4 L h -1 kg -1 for market-age swine . The ~ twofold difference in urinary clearance between heavy sows and market-age swine may contribute to the predicted longer withdrawal interval for penicillin G in the former than in the latter.…”

Pharmacological and pharmacokinetic differences between donkeys and horses

“…They suggested that this dose, administered q.6 to 8 h, should suffice to treat susceptible bacterial infections in both species. However, when comparing values obtained by those authors for horses with others in the literature (Firth et al 1986(Firth et al , 1990 for horses receiving 20,000 iu/kg i.v. sodium penicillin G, the former T 1 /2β‚ was more than 5 times shorter and the apparent volumes of distribution were slightly smaller.…”

“…Therefore, an i.v. dose of 20,000 iu/kg of sodium penicillin G could produce concentrations in plasma above 0.5 iu/ml for about 4 h in donkeys (Oukessou et al 1994), whereas in horses concentrations could be maintained above this for approximately 6 h (Firth et al 1986(Firth et al , 1990. Lack of consistencies and obvious differences in reported values merit further work to establish a suitable dosage regimen for donkeys.…”

Biomedical ethics – antimicrobial responsibility of the equine veterinarian

“…Die Regeln der Kombination von antibiotischen Substanzen und deren Wechselwirkungen untereinander, aber auch mit anderen Substanzen sind zu beachten (Thein 2000, Löscher et al 2010.Wechselwirkungen mit anderen Medikamenten treten z. B. auf bei Sulfonamiden oder mit Trimethoprim potenzierten Sulfonamiden und Flunixin oder beim Einsatz von Phenylbutazon und Penicillin (Firth et al 1990, ElBanna 1999 Im Vergleich zum Abusus von Antibiotika in der Massentierhaltung sowie der auch dort geübten therapeutischen Praxis erscheint das Segment mit diesbezüglicher Relevanz in der Pferdemedizin klein. Gerade deswegen und auch im Interesse der zu erhaltenden Therapiefreiheit wie des Dispensierrechtes sollten die dargestellten Fakten zum Einsatz von Antibiotika ernst genommen und in der täglichen Berufsausübung berük-ksichtigt werden.…”