Prediction of pharmacokinetic profiles of ampicillin sodium, gentamicin sulfate, and combination ampicillin sodium-gentamicin sulfate in serum and synovia of healthy horses

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Abstract
SUMMARY: Pharmacokinetics of ampicillin sodium (11 mg/kg), gentamicin sulfate (2.2 mg/kg), and combination ampicillin sodium-gentamicin sulfate were determined for serum and synovia of healthy horses given single-dose iv injection and were not found to be different from those from other reports; however, a prolonged terminal γ-phase for gentamicin (8,498 ± 1,842 minutes) in serum of horses was found to exist. Pharmacokinetic interaction between combination ampicillin sodium-gentamicin sulfate was not observed in the serum or synovia. Prediction of ampicillin sodium or gentamicin sulfate concentrations in synovia, based on serum-based pharmacokinetics, cannot be accomplished solely upon analysis of peripheral-compartment pharmacokinetics. However, once equilibrium is achieved between synovia and extracellular fluid in the peripheral compartment, the decrease in drug concentrations in synovia parallels that in serum. Therefore, after 6 hours, synovial concentrations of gentamicin sulfate can be predicted based on peripheral-compartment pharmacokinetics, using an appropriate correction factor. The significance of these findings need to be correlated with clinical conditions so that a pharmacostatistical model for the prediction of synovial concentrations of drug(s) during treatment of horses with septic arthritis can be developed.