Lack of gender effect on the pharmacokinetics and pharmacodynamics of dexamethasone in the camel after intravenous administration

Abstract

The pharmacokinetics and pharmacodynamics of dexamethasone were studied in six male and six female camels after a single intravenous dose (0.05 mg kg −1 body weight) of dexamethasone. The pharmacokinetic parameters of the two-compartment pharmacokinetic model for female and male camels, respectively (mean ± SEM) were as follows: terminal elimination half-lives were 8.02 ± 1.15 and 7.33 ± 0.80 h, total body clearances were 95.5 ± 16.0 and 124.5 ± 11.9 ml h −1 per kg, volumes of distribution at steady state were 0.72 ± 0.08 and 0.87 ± 0.14 litre kg −1, and the volumes of the central compartment were 0.12 ± 0.02 and 0.17 ± 0.02 litre kg −1. There was no significant difference in any pharmacokinetic parameter between female and male camels. Pharmacodynamic effects were evaluated by measuring endogenous plasma cortisol, circulating lymphocytes and neutrophils numbers and were analysed using indirect pharmacokinetic/pharmacodynamic models. The estimated IC 50 of dexamethasone for cortisol and lymphocytes for female and male camels were 3.74 ± 0.99 and 2.28 ± 1.09 and 2.63 ± 0.71 and 2.41 ± 0.79 ng ml −1, respectively. The EC 50 for neutrophils for female and male camels were 24.5 ± 5.83 and 20.2 ± 3.82 ng ml −1, respectively. There was no significant difference in any pharmacodynamic parameter between female and male camels. Dexamethasone in urine could be detected for 4–5 days by enzyme-linked immunosorbent assay and for 3–4 days by liquid chromatography/mass spectrometry after an intravenous dose of 0.05 mg kg −1 body weight.