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.
Al Katheeri
N A
NA
Camelracing Laboratory, Forensic Science Laboratory, PO Box 253, Abu Dhabi, United Arab Emirates.
Wasfi
I A
IA
Lambert
M
M
Saeed
A
A
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002162:Camelus / Q000378:metabolism*; D003907:Dexamethasone / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006854:Hydrocortisone / Q000378:metabolism; D007275:Injections, Intravenous / Q000662:veterinary; D008214:Lymphocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D011485:Protein Binding; D012044:Regression Analysis
D001786:Blood Glucose; D003907:Dexamethasone; D006854:Hydrocortisone