Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol
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- 作者：Tuukka Saarikoski ; Teijo I. Saari…
- 关键词：Terbinafine ; Itraconazole ; Tramadol ; O ; desmethyltramadol ; Interaction ; Pharmacokinetics
- 刊名：European Journal of Clinical Pharmacology
- 出版年：2015
- 出版时间：March 2015
- 年：2015
- 卷：71
- 期：3
- 页码：321-327
- 全文大小：472 KB
- 参考文献：1. Moore RA, McQuay HJ (1997) Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. Pain 69(3):287-94 CrossRef
2. Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, Donofrio P, Cornblath D, Sachdeo R, Siu CO, Kamin M (1998) Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology 50(6):1842-846 CrossRef
3. Boureau F, Legallicier P, Kabir-Ahmadi M (2003) Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Pain 104(1-):323-31 CrossRef
4. Malonne H, Coffiner M, Sonet B, Sereno A, Vanderbist F (2004) Efficacy and tolerability of sustained-release tramadol in the treatment of symptomatic osteoarthritis of the hip or knee: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther 26(11):1774-782. doi:10.1016/j.clinthera.2004.11.005 CrossRef
5. Grond S, Sablotzki A (2004) Clinical pharmacology of tramadol. Clin Pharmacokinet 43(13):879-23 CrossRef
6. Gillen C, Haurand M, Kobelt DJ, Wnendt S (2000) Affinity, potency and efficacy of tramadol and its metabolites at the cloned human mu-opioid receptor. Naunyn Schmiedebergs Arch Pharmacol 362(2):116-21 CrossRef
7. Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL, Jacoby HI, Selve N (1993) Complementary and synergistic antinociceptive interaction between the enantiomers of tramadol. J Pharmacol Exp Ther 267(1):331-40
8. Saarikoski T, Saari TI, Hagelberg NM, Neuvonen M, Neuvonen PJ, Scheinin M, Olkkola KT, Laine K (2013) Rifampicin markedly decreases the exposure to oral and intravenous tramadol. Eur J Clin Pharmacol 69(6):1293-301. doi:10.1007/s00228-012-1460-x CrossRef
9. Lintz W, Barth H, Osterloh G, Schmidt-Bothelt E (1986) Bioavailability of enteral tramadol formulations. 1st communication: capsules. Arzneimittelforschung 36(8):1278-283
10. Wu WN, McKown LA, Liao S (2002) Metabolism of the analgesic drug ULTRAM (tramadol hydrochloride) in humans: API-MS and MS/MS characterization of metabolites. Xenobiotica 32(5):411-25. doi:10.1080/00498250110113230 CrossRef
11. Subrahmanyam V, Renwick AB, Walters DG, Young PJ, Price RJ, Tonelli AP, Lake BG (2001) Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. Drug Metab Dispos 29(8):1146-155
12. Poulsen L, Arendt-Nielsen L, Brosen K, Sindrup SH (1996) The hypoalgesic effect of tramadol in relation to CYP2D6. Clin Pharmacol Ther 60(6):636-44. doi:10.1016/S0009-9236(96)90211-8 CrossRef
13. Abdel-Rahman SM, Nahata MC (1997) Oral terbinafine: a new antifungal agent. Ann Pharmacother 31(4):445-56
14. Ahonen J, Olkkola KT, Neuvonen PJ (1995) Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers. Br J Clin Pharmacol 40(3):270-72
15. Abdel-Rahman SM, Gotschall RR, Kauffman RE, Leeder JS, Kearns GL (1999) Investigation of terbinafine as a CYP2D6 inhibitor in vivo. Clin Pharmacol Ther 65(5):465-72. doi:10.1016/S0009-9236(99)70065-2 CrossRef
16. Hynninen VV, Olkkola KT, Bertilsson L, Kurkinen K, Neuvonen PJ, Laine K (2008) Effect of terbinafine and voriconazole on the pharmacokinetics of the antidepressant venlafaxine. Clin Pharmacol Ther 83(2):342-48. doi:10.1038/sj.clpt.6100311
文摘
Background Tramadol is widely used for acute, chronic, and neuropathic pain. Its primary active metabolite is O-desmethyltramadol (M1), which is mainly accountable for the μ-opioid receptor-related analgesic effect. Tramadol is metabolized to M1 mainly by cytochrome P450 (CYP)2D6 enzyme and to other metabolites by CYP3A4 and CYP2B6. We investigated the possible interaction of tramadol with the antifungal agents terbinafine (CYP2D6 inhibitor) and itraconazole (CYP3A4 inhibitor). Methods We used a randomized placebo-controlled crossover study design with 12 healthy subjects, of which 8 were extensive and 4 were ultrarapid CYP2D6 metabolizers. On the pretreatment day 4 with terbinafine (250?mg once daily), itraconazole (200?mg once daily) or placebo, subjects were given tramadol 50?mg orally. Plasma concentrations of tramadol and M1 were determined over 48?h and some pharmacodynamic effects over 12?h. Pharmacokinetic variables were calculated using standard non-compartmental methods. Results Terbinafine increased the area under plasma concentration–time curve (AUC0-?/sub>) of tramadol by 115?% and decreased the AUC0-?/sub> of M1 by 64?% (P--.001). Terbinafine increased the peak concentration (C max) of tramadol by 53?% (P--.001) and decreased the C max of M1 by 79?% (P--.001). After terbinafine pretreatment the elimination half-life of tramadol and M1 were increased by 48 and 50?%, respectively (P--.001). Terbinafine reduced subjective drug effect of tramadol (P--.001). Itraconazole had minor effects on tramadol pharmacokinetics. Conclusions Terbinafine may reduce the opioid effect of tramadol and increase the risk of its monoaminergic adverse effects. Itraconazole has no meaningful interaction with tramadol in subjects who have functional CYP2D6 enzyme.