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

Vet Res Commun. 2004 Aug;28(6):525-42. doi: 10.1023/b:verc.0000040243.30199.1f.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Camelus / metabolism*
  • Dexamethasone / pharmacokinetics*
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Half-Life
  • Hydrocortisone / metabolism
  • Injections, Intravenous / veterinary
  • Lymphocytes / drug effects
  • Neutrophils / drug effects
  • Protein Binding
  • Regression Analysis

Substances

  • Blood Glucose
  • Dexamethasone
  • Hydrocortisone