Opioid Metabolism and Effects of Cytochrome P450

Abstract

years researchers have enhanced our understanding of the metabolism and risk of drug interactions of numerous medications utilized by patients with pain conditions. Pain patients often are prescribed multiple medications that can inhibit or induce specific cytochrome P450 (CYP450) enzymes. This review will focus on the effect of the CYP450 enzyme system metabolism on opioid agents codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and oxymorphone, as well as the potential effect of these opioids on the metabolism of other medications and vice versa.

A Simple Liquid Chromatography–Tandem Mass Spectrometry Method for Determination of Plasma Fentanyl Concentration in Rats and Patients with Cancer Pain

“…Its plasma concentration may therefore vary as a result of physiologically reduced CYP3A4 activity in the liver (liver disease and aging) or co-administration of drugs either inducing or inhibiting CYP3A4. 9,10) As outlined above, individual differences in the plasma concentrations of fentanyl is likely to occur when applied to the skin because of the dosage form and metabolic characteristics of the drug itself.…”

Safety of opioid patch initiation in Australian residential aged care

“…For example, the proportion of ultrarapid metabolisers is higher (up to 29%) in Middle Eastern and Northern African populations, and lower (0.5%) in Asians (Stamer & Stuber, 2007); the proportion of poor metabolisers is lower in Asians and African Americans (Holmquist, 2009).…”

“…It is metabolised in the liver primarily to noroxycodone and oxymorphone, but these metabolites have clinically negligible analgesic effects (Lalovic et al, 2006;. Oxymorphone, the production of which relies on CYP2D6, is more potent than oxycodone, but plasma concentrations are low; noroxycodone, the major metabolite and the production of which relies on CYP3A4, is only weakly active (Coluzzi & Mattia, 2005;Lalovic et al, 2006;Holmquist, 2009). Unlike codeine, inhibition of CYP2D6 with quinine does not reduce the analgesic effect of oxycodone (Lalovic et al, 2006).…”

“…Other substrates of p-glycoprotein, one of the main efflux transporters, include methadone and fentanyl (Sweeney, 2007). As well as morphine, UGT2B7 also mediates the metabolism and formation of glucuronides from other opioids including buprenorphine, codeine, dihydrocodeine and hydromorphone, but the clinical significance of UGT2B7 gene variants has not yet been well defined (Somogyi et al, 2007;Holmquist, 2009). …”

The Prevalence of Opioid-Related Major Potential Drug-Drug Interactions and Their Impact on Health Care Costs in Chronic Pain Patients

“…6 Co-administration of CYP450 inducers or inhibitors may result in pDDIs and affect a patient's safety. Small clinical studies of oxycodone pDDIs have demonstrated pharmacokinetic changes and associated clinical manifestations.…”