CYP3A5*3 affects plasma disposition of noroxycodone and dose escalation in cancer patients receiving oxycodone.

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Naito T, Takashina Y, Yamamoto K, Tashiro M, Ohnishi K, Kagawa Y, Kawakami J

CYP3A5*3 affects plasma disposition of noroxycodone and dose escalation in cancer patients receiving oxycodone.

J Clin Pharmacol. 2011 Nov;51(11):1529-38. doi: 10.1177/0091270010388033. Epub 2011 Jan 5.

PubMed ID

21209234 [ View in PubMed

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Abstract

The aim of this study was to evaluate the plasma dispositions of oxycodone and its demethylates and dose escalation based on genetic polymorphisms of CYP2D6, CYP3A5, ABCB1, and OPRM1 in cancer patients receiving oxycodone. Sixty-two Japanese cancer patients receiving oxycodone extended-release tablets were enrolled. Predose plasma concentrations (C(12)) of oxycodone, noroxycodone, and oxymorphone were determined at the titrated dose. Daily oxycodone escalation rate was evaluated as the opioid escalation index (OEI). Genetic variants did not significantly alter oxycodone C(12). Oxymorphone C(12) and its ratio to oxycodone C(12) were significantly higher in CYP2D6 extensive metabolizers than in intermediate metabolizers but did not affect dose escalation. In contrast, noroxycodone C(12) and its ratio to oxycodone C(12) were significantly higher in the CYP3A5*1 carrier group than in the *3/*3 group. The OEI was significantly higher in the CYP3A5*3/*3 group than in the *1 carrier group. No significant difference was observed in the OEI in the other genetic variants. Noroxycodone C(12) was higher in the dose escalation group as compared to the nonescalation group and significantly affected the incidence of dose escalation. In conclusion, CYP3A5*3 altered the plasma disposition of noroxycodone, which was inversely affecting the dose escalation in cancer patients receiving oxycodone.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Oxycodone	Cytochrome P450 3A5	Protein	Humans	Unknown	Substrate	Details