Effects of itraconazole on the pharmacokinetics and pharmacodynamics of intravenously and orally administered oxycodone

Background The aim of this study was to investigate the effects of the cytochrome P450 3A4 (CYP34A) inhibitor itraconazole on the pharmacokinetics and pharmacodynamics of orally and intravenously administered oxycodone. Methods Twelve healthy subjects were administered 200 mg itraconazole or placebo...

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Bibliographic Details
Published in:European journal of clinical pharmacology 2010-04, Vol.66 (4), p.387-397
Main Authors: Saari, Teijo I, Grönlund, Juha, Hagelberg, Nora M, Neuvonen, Mikko, Laine, Kari, Neuvonen, Pertti J, Olkkola, Klaus T
Format: Article
Language:English
Subjects:
Analgesics, Opioid - administration & dosage
Analgesics, Opioid - pharmacokinetics
Analgesics, Opioid - pharmacology
Area Under Curve
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cross-Over Studies
CYP enzymes
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP3A Inhibitors
Drug therapy
Humans
Injections, Intravenous
Intravenous/oral drug administration
itraconazole
Itraconazole - administration & dosage
Itraconazole - pharmacokinetics
Itraconazole - pharmacology
Kinetics
Medical sciences
Morphinans - pharmacokinetics
Morphinans - pharmacology
Opioid effects
Oxidation-Reduction
Oxycodone
Oxycodone - administration & dosage
Oxycodone - pharmacokinetics
Oxycodone - pharmacology
Oxymorphone - pharmacokinetics
Oxymorphone - pharmacology
pharmacokinetics
Pharmacokinetics and Disposition
Pharmacology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Side effects
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Summary:Background The aim of this study was to investigate the effects of the cytochrome P450 3A4 (CYP34A) inhibitor itraconazole on the pharmacokinetics and pharmacodynamics of orally and intravenously administered oxycodone. Methods Twelve healthy subjects were administered 200 mg itraconazole or placebo orally for 5 days in a four-session paired cross-over study. On day 4, oxycodone was administered intravenously (0.1 mg/kg) in the first part of the study and orally (10 mg) in the second part. Plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h, and pharmacodynamic effects were evaluated. Results Itraconazole decreased plasma clearance (Cl) and increased the area under the plasma concentration-time curve (AUC0-∞) of intravenous oxycodone by 32 and 51%, respectively (P 
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-009-0775-8