Pharmacokinetics of chloramphenicol base in horses and comparison to compounded formulations

Abstract

Chloramphenicol is commonly used in horses; however, there are no studies evaluating the pharmacokinetics of veterinary canine‐approved tablets. Studies using different formulations and earlier analytical techniques led to concerns over low bioavailability in horses. Safety concerns about human health have led many veterinarians to prescribe compounded formulations that are already in suspension or paste form. The objective of this study was to evaluate the pharmacokinetics of approved chloramphenicol tablets in horses, along with compounded preparations. The hypothesis was that chloramphenicol has low absorption and a short half‐life in horses leading to low serum concentrations and that compounded preparations have lower relative bioavailability. Seven horses were administered chloramphenicol tablets (50 mg/kg orally). In a crossover design, they were administered two compounded preparations to compare all three formulations at the same dose (50 mg/kg). Cmax was 5.25 ± 4.07 μg/ml at 4.89 hr, 4.96 ± 3.31 μg/ml at 4.14 hr, and 3.84 ± 2.96 μg/ml at 4.39 hr for the tablets, paste, and suspension, respectively. Elimination half‐life was 2.65 ± 0.75, 3.47 ± 1.47, and 4.36 ± 4.54 hr for tablets, paste, and suspension, respectively. The AUC0→∞ was 17.93 ± 7.69, 16.25 ± 1.85, and 14.00 ± 5.47 hr*μg/ml for the tablets, compounded paste, and compounded suspension, respectively. Relative bioavailability of compounded suspension and paste was 78.1% and 90.6%. Cmax after administration of all formulations did not reach the recommended MIC target of 8 μg/ml set by the Clinical Laboratory Standards Institute (CLSI) for most bacteria. Multidose studies are warranted, but the low serum concentrations suggest that bacteria with MIC values lower than CLSI recommendations should be targeted in adult horses.

Genetic analysis of the equine orthologues for human CYP2D6: unraveling the complexity of the CYP2D family in horses

“…The acquisition of pharmacogenetic knowledge is not limited to human genetics but is also echoed in veterinary medicine. Horses are among the companion and sport animals that can be widely treated with drugs such as NSAIDs (2)(3)(4), corticosteroids (5,6), local anesthetics (7,8), mucolytics (9), sedatives (10), antibiotics (11)(12)(13), diuretics (14)(15)(16) and PPIs (17,18). In addition to certain medications that are banned in racehorses, others may be administered as needed, but are subject to control through drug testing.…”