Rifampin greatly reduces the plasma concentrations of intravenous and oral oxycodone.
BACKGROUND
Oxycodone is a mu-opioid receptor agonist that is metabolized mainly in the liver by cytochrome P450 3A and 2D6 enzymes. Rifampin is a strong inducer of several drug-metabolizing enzymes. The authors studied the interaction of rifampin with oxycodone. Their hypothesis was that rifampin enhances the CYP3A-mediated metabolism of oxycodone and attenuates its pharmacologic effect.


METHODS
The protocol was a four-session, paired crossover. Twelve volunteers were given 600 mg oral rifampin or placebo once daily for 7 days. Oxycodone was given on day 6. In the first part of the study, 0.1 mg/kg oxycodone hydrochloride was given intravenously. In the second part of the study, 15 mg oxycodone hydrochloride was given orally. Concentrations of oxycodone and its metabolites noroxycodone, oxymorphone, and noroxymorphone were determined for 48 h. Psychomotor effects were characterized for 12 h by several visual analog scales. Analgesic effects were characterized by measuring the heat pain threshold and cold pain sensitivity.


RESULTS
Rifampin decreased the area under the oxycodone concentration-time curve of intravenous and oral oxycodone by 53% and 86%, respectively (P < 0.001). Oral bioavailability of oxycodone was decreased from 69% to 21% (P < 0.001). Rifampin greatly increased the plasma metabolite-to-parent drug ratios for noroxycodone and noroxymorphone (P < 0.001). Pharmacologic effects of oral oxycodone were attenuated.


CONCLUSIONS
Induction of cytochrome P450 3A by rifampin reduced the area under the oxycodone concentration-time curve of intravenous and oral oxycodone. The pharmacologic effects of oxycodone were modestly attenuated. To maintain adequate analgesia, dose adjustment of oxycodone may be necessary, when used concomitantly with rifampin.
Nieminen
Tuija H
TH
Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University Hospital, Turku, Finland. tuija.nieminen@utu.fi
Hagelberg
Nora M
NM
Saari
Teijo I
TI
Pertovaara
Antti
A
Neuvonen
Mikko
M
Laine
Kari
K
Neuvonen
Pertti J
PJ
Olkkola
Klaus T
KT
D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001682:Biological Availability; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010098:Oxycodone / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D012293:Rifampin / Q000009:adverse effects*; D055815:Young Adult
D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D010098:Oxycodone; D051544:Cytochrome P-450 CYP3A; D012293:Rifampin