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Rifampin greatly reduces the plasma concentrations of intravenous and oral oxycodone

Tuija H Nieminen1, Nora M Hagelberg, Teijo I Saari

  • 1Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University Hospital, Turku, Finland. tuija.nieminen@utu.fi

Anesthesiology
|May 7, 2009
PubMed
Abstract

Insights

Rifampin significantly reduces oxycodone levels by inducing CYP3A enzymes, potentially requiring dose adjustments for effective pain relief. This interaction impacts oxycodone metabolism and its analgesic effects.

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Clinical Pharmacology

Background:

  • Oxycodone, a mu-opioid agonist, is primarily metabolized by hepatic cytochrome P450 (CYP) enzymes 3A and 2D6.
  • Rifampin is a potent inducer of various drug-metabolizing enzymes, including CYP3A.
  • The study investigated the pharmacokinetic and pharmacodynamic interaction between rifampin and oxycodone.

Purpose of the Study:

  • To determine if rifampin enhances CYP3A-mediated metabolism of oxycodone.
  • To assess the impact of rifampin on the pharmacologic effects of oxycodone.
  • To evaluate the clinical implications of this drug interaction.

Main Methods:

  • A four-session, paired crossover study involving 12 healthy volunteers.
  • Administration of oral rifampin (600 mg daily) or placebo for 7 days.
  • Oxycodone administration (intravenous or oral) on day 6, with pharmacokinetic and pharmacodynamic assessments.

Main Results:

  • Rifampin decreased the area under the oxycodone concentration-time curve by 53% (IV) and 86% (oral) (P < 0.001).
  • Oral bioavailability of oxycodone was reduced from 69% to 21% (P < 0.001).
  • Increased plasma metabolite-to-parent drug ratios and attenuated pharmacologic effects of oxycodone were observed.

Conclusions:

  • CYP3A induction by rifampin significantly reduces systemic exposure to oxycodone.
  • The pharmacologic effects of oxycodone are modestly attenuated.
  • Oxycodone dosage adjustments may be necessary when co-administered with rifampin to ensure adequate analgesia.

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