Effects of ketoconazole on the pharmacokinetics and pharmacodynamics of morphine in healthy Greyhounds.
OBJECTIVE
To assess pharmacokinetics and pharmacodynamics of morphine and the effects of ketoconazole on the pharmacokinetics and pharmacodynamics of morphine in healthy Greyhounds.


METHODS
6 healthy Greyhounds, 3 male and 3 female.


METHODS
Morphine sulfate (0.5 mg/kg. IV) was administered to Greyhounds prior to and after 5 days of ketoconazole (12.7 +/- 0.6 mg/kg, PO) treatment. Plasma samples were obtained from blood samples that were collected at predetermined time points for measurement of morphine and ketoconazole concentrations by mass spectrometry. Pharmacokinetics of morphine were estimated by use of computer software.


RESULTS
Pharmacodynamic effects of morphine in Greyhounds were similar to those of other studies in dogs and were similar between treatment groups. Morphine was rapidly eliminated with a half-life of 1.28 hours and a plasma clearance of 32.55 mL/min/kg. The volume of distribution was 3.6 L/kg. No significant differences in the pharmacokinetics of morphine were found after treatment with ketoconazole. Plasma concentrations of ketoconazole were high and persisted longer than expected in Greyhounds.


CONCLUSIONS
Ketoconazole had no significant effect on morphine pharmacokinetics, and the pharmacodynamics were similar between treatment groups. Plasma concentrations of ketoconazole were higher than expected and persisted longer than expected in Greyhounds.
Kukanich
Butch
B
Department of Anatomy and Physiology, and Pharmacology, Clinical, Analytical and Toxicological Services (PharmCATS), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Borum
Stacy L
SL
D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D004285:Dogs / Q000097:blood / Q000378:metabolism*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D007654:Ketoconazole / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D009020:Morphine; D007654:Ketoconazole