Determination of the pharmacokinetic parameters of 4 formulations of benzylpenicillin
Lallemand EA*1, Bousquet-Melou A1, Chapuis L1, Ferran AA1, Kuroda T2, Lacroix MZ1, Ramon-Portugal F1, Roques BB1, Toutain P-L3
1INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France, 2Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan, 3The Royal Veterinary College, Hatfiled, United Kingdom.
Objectives:
Benzylpenicillin (BP) is a first-line antibiotic for equine practitioners but there are discrepancies between manufacturers’ and scientific recommendations regarding doses and intervals. The objective of our study was to determine the pharmacokinetic (PK) parameters of BP using 4 different formulations, allowing determination of appropriate dosing regimens.
Methods:
An experimental PK 3x3 crossover study was performed on six healthy horses (3geldings, 3mares; 8+/-3yo; 503+/-40kg) receiving commercial formulations of BP IM: Depocilline® (BPprocaine, 10mg/kgBP Day1to3), Duplocilline® (BPprocaine and BPbenzathine, 12,4mg/kgBP Day1and3), Penetavet® (penethamate hydroiodide, 6gBP Day1, 3gBP Day2and3). A single BPsodium IV dose was administered (BP-Na, 12,4mg/kgBP). BP concentrations in blood samples were analyzed by UPLC and a 3-compartment analysis was performed (Phoenix®WinNonlin®8.3). The PK/PD indice T>MIC was determined using MICs of target pathogens. Tolerance was evaluated. The study was approved by the institutional animal care committee.
Results:
Except one horse that exhibited a minor neurological reaction at first Penetavet® injection, all other injections were well tolerated, with a maximal observed pain score of 4/21. Estimated muscle lysis was more important with Penetavet® compared to Depocilline® or Duplocilline®. BP PK parameters were calculated and bioavailabilities of BP were 100% for Depocilline®, 82% for BPprocaine and 100% for BPbenzathine in Duplocilline®, and 69% for Penetavet®.
Conclusions:
Using the manufacturers dosing regimens, BP plasma concentrations ensured higher T>MIC values with Depocilline compared to Duplocilline and Penetavet. Knowledge of BP pharmacokinetic profiles and of MICs of target bacteria allows to ascertain more adequate dosing regimens able to cure equine patients.