Pharmacokinetics and pharmacodynamics of dexamethasone after intravenous administration in camels: Effect of dose

The pharmacokinetics and pharmacodynamics of dexamethasone were evaluated in healthy camels after single intravenous bolus doses of 0.05, 0.1 and 0.2 mg/kg body weight. Dexamethasone showed dose-independent pharmacokinetics. The pharmacokinetic parameters of the two-compartment pharmacokinetic model for the lowest intravenous dose (mean±SD) were as follows: terminal elimination half-life 8.17±1.79 h; total body clearance 100.7±52.1 (ml/h)/kg; volume of distribution at steady state 0.95±0.23 L/kg; and volume of the central compartment 0.22±0.07 L/kg. The extent of plasma protein binding was linear over the concentration range 5-100 ng/ml and averaged 75%±2%. Pharmacodynamic effects were evaluated by measuring endogenous plasma cortisol concentrations, numbers of circulating lymphocytes and neutrophils and plasma glucose concentrations and were analysed using indirect pharmacokinetic/pharmacodynamic models. The cumulative systemic effect increased with dose for markers of pharmacodynamic activity. The estimated IC50 of dexamethasone for cortisol and lymphocytes for the lowest dose were 3.74±2.44 and 5.58± 8.37 ng/ml, respectively and the EC50 values for neutrophils and glucose were 45.8±36.9 and 1.17±0.71 ng/ml, respectively. © 2004 Kluwer Academic Publishers.