Plasma and synovial fluid pharmacokinetics of a single intravenous dose of meropenem in adult horses

The objective of this study was to determine the pharmacokinetics of meropenem in horses after intravenous (IV) administration. A single IV dose of meropenem was administered to six adult horses at 10 mg/kg. Plasma and synovial fluid samples were collected for 6 hr following administration. Meropenem concentrations were determined by bioassay. Plasma and synovial fluid data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean +/- SD values for elimination half-life, volume of distribution at steady-state, and clearance after IV administration for plasma samples were 0.78 +/- 0.176 hr, 136.1 +/- 19.69 ml/kg, and 165.2 +/- 29.72 ml hr(-1) kg(-1), respectively. Meropenem in synovial fluid had a slower elimination than plasma with a terminal half-life of 2.4 +/- 1.16 hr. Plasma protein binding was estimated at 11%. Based on a 3-compartment open pharmacokinetic model of simultaneously fit plasma and synovial fluid, dosage simulations were performed. An intermittent dosage of meropenem at 5 mg/kg IV every 8 hr or a constant rate IV infusion at 0.5 mg/kg per hour should maintain adequate time above the MIC target of 1 mu g/ml. Carbapenems are antibiotics of last resort in humans and should only be used in horses when no other antimicrobial would likely be effective.