A1 Refereed original research article in a scientific journal
Effect of Telithromycin on the Pharmacokinetics and Pharmacodynamics of Oral Oxycodone
Authors: Gronlund J, Saari T, Hagelberg N, Martikainen IK, Neuvonen PJ, Olkkola KT, Laine K
Publisher: SAGE PUBLICATIONS INC
Publication year: 2010
Journal: Journal of Clinical Pharmacology
Journal name in source: JOURNAL OF CLINICAL PHARMACOLOGY
Journal acronym: J CLIN PHARMACOL
Number in series: 1
Volume: 50
Issue: 1
First page : 101
Last page: 108
Number of pages: 8
ISSN: 0091-2700
DOI: https://doi.org/10.1177/0091270009336444
Abstract
The aim of this study is to determine whether the inhibition of CYP2D6 and CYP3A4 enzyme activity with telithromycin affects the pharmacokinetics and pharmacodynamics of orally administered oxycodone in a randomized 2-phase crossover study. Eleven healthy subjects were pretreated with 800 mg of oral telithromycin or placebo for 4 days. On day 3, they ingested 10 mg of immediate-release oxycodone. Plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 hours, and pharmacodynamic effects were evaluated. Telithromycin increased the area under the plasma concentration-time curve (AUC(0-infinity)) of oxycodone by 80% (P < .001) and reduced the AUC(0-infinity) of noroxycodone by 46% (P < .001). Most of the pharmacokinetic changes were seen in the elimination phase, with little effect by telithromycin on the peak concentration of oxycodone. Pharmacodynamic effects of oxycodone were modestly enhanced by telithromycin. In conclusion, telithromycin clearly reduces the N-demethylation of oxycodone to noroxycodone by inhibiting the CYP450 3A4 enzyme. The use of telithromycin in patients receiving multiple doses of oxycodone for pain relief may increase the risk of opioid adverse effects. Reduction of oxycodone dose by 25% to 50% followed by readjustment according to the clinical response might be appropriate.
The aim of this study is to determine whether the inhibition of CYP2D6 and CYP3A4 enzyme activity with telithromycin affects the pharmacokinetics and pharmacodynamics of orally administered oxycodone in a randomized 2-phase crossover study. Eleven healthy subjects were pretreated with 800 mg of oral telithromycin or placebo for 4 days. On day 3, they ingested 10 mg of immediate-release oxycodone. Plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 hours, and pharmacodynamic effects were evaluated. Telithromycin increased the area under the plasma concentration-time curve (AUC(0-infinity)) of oxycodone by 80% (P < .001) and reduced the AUC(0-infinity) of noroxycodone by 46% (P < .001). Most of the pharmacokinetic changes were seen in the elimination phase, with little effect by telithromycin on the peak concentration of oxycodone. Pharmacodynamic effects of oxycodone were modestly enhanced by telithromycin. In conclusion, telithromycin clearly reduces the N-demethylation of oxycodone to noroxycodone by inhibiting the CYP450 3A4 enzyme. The use of telithromycin in patients receiving multiple doses of oxycodone for pain relief may increase the risk of opioid adverse effects. Reduction of oxycodone dose by 25% to 50% followed by readjustment according to the clinical response might be appropriate.
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