Effect of inhibition of cytochrome P450 enzymes 2D6 and 3A4 on the pharmacokinetics of intravenous oxycodone: A randomized, three-phase, crossover, placebo-controlled study

Clinical Drug Investigation

Volumn 31, Issue 3, 2011, Pages 143-153

  Grönlund, Juha ^a   Saari, Teijo I ^a   Hagelberg, Nora M ^a   Neuvonen, Pertti J ^b   Laine, Kari ^c   Olkkola, Klaus T ^a  

^a TURKU UNIVERSITY HOSPITAL   (Finland)

^b UNIVERSITY OF HELSINKI   (Finland)

^c UNIVERSITY OF TURKU   (Finland)

Author keywords

Analgesics, pharmacokinetics; Cytochrome P450; Itraconazole, therapeutic use; Oxycodone, pharmacokinetics; Paroxetine, therapeutic use

Indexed keywords

CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; ITRACONAZOLE; NALOXONE; OXYCODONE; OXYMORPHONE; PAROXETINE; PLACEBO;

ADULT; ARTICLE; CLINICAL ARTICLE; COLD TOLERANCE; CROSSOVER PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG ELIMINATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG INHIBITION; FEMALE; GENOTYPE; HUMAN; HUMAN EXPERIMENT; MALE; NAUSEA; NORMAL HUMAN; PAIN THRESHOLD; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION;

ADULT; ANALGESICS, OPIOID; CROSS-OVER STUDIES; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; DRUG INTERACTIONS; ENZYME INHIBITORS; FEMALE; HALF-LIFE; HUMANS; ITRACONAZOLE; MALE; OXYCODONE; PAROXETINE; YOUNG ADULT;

EID: 79751502059     PISSN: 11732563     EISSN: 11791918     Source Type: Journal    
DOI: 10.2165/11539950-000000000-00000     Document Type: Article

References (34)

1. Lalovic B, Phillips B, Risler LL, et al. Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and in (Pubitemid 38420280)
2. Dresser GK, Spence JD, Bailey DG. Pharmacokineticpharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 2000; 38: 41-57 (Pubitemid 30055093)
3. Olkkola KT, Isohanni MH, Hamunen K, et al. The effect of erythromycin and fluvoxamine on the pharmacokinetics of intravenous lidocaine. Anesth Analg 2005; 100: 1352-6 (Pubitemid 40577383)
4. Jokinen MJ, Ahonen J, Neuvonen PJ, et al. The effect of erythromycin, fluvoxamine, and their combination on the pharmacokinetics of ropivacaine. Anesth Analg 2000; 91: 1207-12
5. Grönlund J, Saari TI,Hagelberg NM, et al. Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone. Br J Clin Pharmacol 2010; 70: 78-87
6. Doherty MM, Charman WN. The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism? Clin Pharmacokinet 2002; 41: 235-53 (Pubitemid 34533755)
7. Pöyhiä R, Olkkola KT, Seppälä T, et al. The pharmacokinetics of oxycodone after intravenous injection in adults. Br J Clin Pharmacol 1991; 32: 516-8
8. Pöyhiä R, Seppälä T, Olkkola KT, et al. The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects. Br J Clin Pharmacol 1992; 33: 617-21
9. Michna E, Ross EL, HynesWL, et al. Predicting aberrant drug behavior in patients treated for chronic pain: importance of abuse history. J Pain Symptom Manage 2004; 28: 250-8 (Pubitemid 39158807)
10. Chu S, Metcalfe CD. Analysis of paroxetine, fluoxetine and norfluoxetine in fish tissues using pressurized liquid extraction, mixed mode solid phase extraction cleanup and liquid chromatography-tandem mass spectrometry. J Chromatogr 2007; 1163: 112-8 (Pubitemid 47247703)
11. Gubbins PO, Gurley BJ, Bowman J. Rapid and sensitive high performance liquid chromatographic method for the determination of itraconazole and its hydroxy-metabolite in human serum. J Pharm Biomed Anal 1998; 16: 1005-12 (Pubitemid 28139037)
12. Neuvonen M, Neuvonen PJ. Determination of oxycodone, noroxycodone, oxymorphone, and noroxymorphone in human plasma by liquid chromatography- electrospraytandem mass spectrometry. Ther Drug Monit 2008; 30: 333-40
13. Sistonen J, Fuselli S, Levo A, et al. CYP2D6 genotyping by a multiplex primer extension reaction. Clin Chem 2005; 51: 1291-5 (Pubitemid 43079419)
14. Bond A, Lader M. Use of analog scales in rating subjective feelings. Br J Med Psychol 1974; 47: 211-8
15. Cogan DG. Simplified entopic pupillometer. Am J Ophthalmol 1941; 24: 1431-3
16. Hannington-Kiff JG. Measurement of recovery from outpatient general anaesthesia with a simple ocular test. Br Med J 1970; 3: 132-5
17. Stone BM. Pencil and paper tests: sensitivity to psychotropic drugs. Br J Clin Pharmacol 1984; 18 Suppl. 1: 15S-20S (Pubitemid 15184100)
18. Staahl C, Drewes AM. Experimental human pain models: a review of standardised methods for preclinical testing of analgesics. Basic Clin Pharmacol Toxicol 2004; 95: 97-111 (Pubitemid 39331302)
19. Lalovic B, Kharasch E, Hoffer C, et al. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clin Pharmacol Ther 2006; 79: 461-79
20. Saari TI, Gronlund J, Hagelberg NM, et al. Effects of itraconazole on the pharmacokinetics and pharmacodynamics of intravenously and orally administered oxycodone. Eur J Clin Pharmacol 2010; 66: 387-97
21. Heiskanen T, Olkkola KT, Kalso E. Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Clin Pharmacol Ther 1998; 64: 603-11 (Pubitemid 29011380)
22. Zwisler ST, Enggaard TP, Mikkelsen S, et al. Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesia. Acta Anaesthesiol Scand 2010; 54: 232-40
23. Saari TI, Laine K, Leino K, et al. Effect of voriconazole on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Clin Pharmacol Ther 2006; 79: 362-70
24. Leow KP, Smith MT, Williams B, et al. Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer. Clin Pharmacol Ther 1992; 52: 487-95
25. Olkkola KT, Aranko K, Luurila H, et al. A potentially hazardous interaction between erythromycin and midazolam. Clin Pharmacol Ther 1993; 53: 298-305 (Pubitemid 23094372)
26. Isohanni MH, Neuvonen PJ, Palkama VJ, et al. Effect of erythromycin and itraconazole on the pharmacokinetics of intravenous lignocaine. Eur J Clin Pharmacol 1998; 54: 561-5 (Pubitemid 28487378)
27. Isohanni MH, Neuvonen PJ, Olkkola KT. Effect of erythromycin and itraconazole on the pharmacokinetics of oral lignocaine. Pharmacol Toxicol 1999; 84: 143-6 (Pubitemid 29129854)
28. Kato M. Intestinal first-pass metabolism of CYP3A4 substrates. Drug Metab Pharmacokinet 2008; 23: 87-94
29. Grönlund J, Saari T, Hagelberg N, et al. Effect of telithromycin on the pharmacokinetics and pharmacodynamics of oral oxycodone. J Clin Pharmacol 2010; 50: 101-8
30. Hagelberg NM, Nieminen TH, Saari TI, et al. Voriconazole drastically increases exposure to oral oxycodone. Eur J Clin Pharmacol 2009; 65: 263-71
31. Schmitt JA, Riedel WJ, Vuurman EF, et al. Modulation of the critical flicker fusion effects of serotonin reuptake inhibitors by concomitant pupillary changes. Psychopharmacology (Berl) 2002; 160: 381-6 (Pubitemid 34253280)
32. Erjavec MK, Coda BA, Nguyen Q, et al. Morphine-fluoxetine interactions in healthy volunteers: analgesia and side effects. J Clin Pharmacol 2000; 40: 1286-95
33. Lemberg KK, Heiskanen TE, Neuvonen M, et al. Does coadministration of paroxetine change oxycodone analgesia: an interaction study in chronic pain patients. Scand J Pain 2010; 1: 24-33
34. Koltzenburg M, Pokorny R, Gasser UE, et al. Differential sensitivity of three experimental pain models in detecting the analgesic effects of transdermal fentanyl and buprenorphine. Pain 2006; 126: 165-74 (Pubitemid 44802773)