Tramadol in Japanese Population: the Relative Contribution of M1 Metabolite as Assessed by <i>CYP</i>2<i>D</i>6</i>*10 Genotype — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Tramadol in Japanese Population: the Relative Contribution of M1 Metabolite as Assessed by <i>CYP</i>2<i>D</i>6</i>*10 Genotype
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, U.S.A.
1 Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, U.S.A.
Several preclinical and clinical studies suggested that tramadol has a multi-mechanistic analgesic action. Upon in vitro evaluation, tramadol parent drug was determined to have only very weak affinity for opioid receptors. Metabolism via CYP2D6, though, yields the O -desmethyl metabolite (M1), which has much greater opioid receptor affinity. In tests in animals and human volunteers, tramadol’s analgesic effect is only partially blocked by the opioid antagonist naloxone. Yet the contribution of parent drug to analgesia is still debated. Observance of good analgesic response to tramadol in Japanese and other Asian populations that express the CYP 2 D 6*10 genotype suggests that parent drug accounts for the majority of tramadol’s analgesic effect in most clinical settings. Understanding of tramadol’s multi-mechanistic action continues to form the basis for understanding its clinical attributes.
R. B. Raffa and E. Friderichs, “The Basic Science Aspect of Tramadol Hydrochloride,” Pain Reviews, Vol. 3, 1996, pp. 249-271.
T. Itoh, “Control of Non-Malignant Chronic Pain Conditions in Japan and the Possible Future Role of Tramadol,” European Journal of Pain, Vol. 5, Suppl. A, 2001, pp. 87-89.
S. Saeki, “Indication and Usage of Opioids Except Morphine for Chronic Non-Malignant Intractable Pain,” Masui, Japanese Journal of Anesthesiology, Vol. 57, No. 11, 2008, pp. 1351-1358.
T. Yanagita, “Drug Dependence Potential of 1-(M-meth- oxy-phenyl)-2-dimethylaminomethyl)-cyclohexan-1-ol- hydrochloride (Tramadol) Tested in Monkeys,” Arzneim-it-telforschung, Vol. 28, No. 1a, 1978, pp. 158-163.
K. Mimami, “Recent Evidences in the Pharmacological Mechanisms of the Tramadol,” Masui, Japanese Journal of Anesthesiology, Vol. 54, No. 11, 2005, pp. 1224-1233.
C. Li, S. Q. Chen, B. X. Chen, W. Q. Huang and K. X. Liu, “The Antinociceptive Effect of In-trathecal Tramadol in Rats: The Role of Alpha 2-Adrenoceptors in the Spinal Cord,” Journal of Anesthesia, Vol. 25, No. 2, 2012, pp. 230-235.
K. Minami, T. Yokoyama, J. Ogata and Y. Uezono, “The Tramadol Metabolite O-Desmethyl Tramadol Inhibits Substance P-Receptor Functions Expressed in Xenopus Oocytes,” Journal of Pharmacological Sciences, Vol. 115, No. 3, 2011, pp. 421-424. doi:10.1254/jphs.10313SC
Y. Yamazoe and K. Nagata, “Genetic Polymorphism in Human Drug Metabolism,” Nihon Yakurigaku Zasshi, Vol. 101, No. 2, 1993, pp. 69-77. doi:10.1254/fpj.101.2_69
T. Yokoi and T. Kamataki, “Genetic Polymorphism of Drug Metabolizing Enzymes: New Mutations in CYP2D6 and CYP2A6 Genes in Japa-nese,” Nihon Yakurigaku Zasshi, Vol. 112, No. 1, 1998, pp. 5-14. doi:10.1254/fpj.112.5
M. Chida, T. Yokoi, Y. Kosaka, K. Chiba, H. Nakamura, T. Ishizaki, J. Yokota, M. Kinoshita, K. Sato, M. Inaba, Y. Aoki, F. J. Gonzalez and T. Kamataki, “Genetic Polymorphism of CYP2D6 in the Japanese Population,” Pharmacogenetics, Vol. 9, No. 5, 1999, pp. 601-605.
Y. Mitsunaga, T. Kubota, A. Ishiguro, Y. Yamada, H. Sasaki, K. Chiba and T. Iga, “Frequent Occurrence of CYP2D6*10 Duplication Allele in a Japanese Population,” Mutation Research, Vol. 505, No. 1-2, 2002, pp. 83-85. doi:10.1016/S0027-5107(02)00122-7
M. Kitada, “Genetic Polymorphism of Cytochrome P450 Enzymes in Asian Populations: Focus on CYP2D6,” International Journal Clinical Pharmacology Research, Vol. 23, No. 1, 2003, pp. 31-35.
T. Mizutani, “PM Frequencies of Major CYPs in Asians and Caucasians,” Drug Metabol-ism Reviews, Vol. 35, No. 2-3, 2003, pp. 99-106. doi:10.1081/DMR-120023681
B. Schmid, J. Bircher, R. Preisig and A. Kupfer, “Poly- morphic Dextromethor-phan Metabolism: Co-Segregation of Oxidative O-Demethylation with Debrisoquin Hydroxylation,” Clinical Pharmacology & Therapeutics, Vol. 38, No. 6, 1985, pp. 618-624. doi:10.1038/clpt.1985.235
N. Nagai, T. Kawakubo, F. Kaneko, M. Ishii, R. Shino- hara, Y. Saito, H. Shima-mura, A. Ohnishi and H. Ogata, “Pharmacokinetics and Polymorphic Oxidation of Dextromethorphan in a Japa-nese Population,” Biopharmaceutics & Drug Disposition, Vol. 17, No. 5, 1996, pp. 421- 433. doi:10.1002/(SICI)1099-081X(199607)17:5 3.0.CO;2-9
Y. Ikenaga, T. Fukuda, K. Fu-kuda, Y. Nishida, M. Naohara, H. Maune and J. Azuma, “The Frequency of Candidate Alleles for CYP2D6 Geno-typing in the Japanese Population with an Additional Respect to the –1584C to G Substitution,” Drug Metabolism and Pharmacokinetics, Vol. 20, No. 2, 2005, pp. 113-116. doi:10.2133/dmpk.20.113
A. Ebisawa, M. Hiratsuka, K. Sakuyama, Y. Konno, T. Sasaki and M. Mizugaki, “Two Novel Single Nucleotide Polymorphisms (SNPs) of the CYP2D6 Gene in Japanese Individuals,” Drug Meta-bolism and Pharmacokinetics, Vol. 20, No. 4, 2005, pp. 294-299. doi:10.2133/dmpk.20.294
H. Yokota, S. Tamura, H. Furuya, S. Kimura, M. Watanabe, I. Kanazawa, I. Kondo and F. J. Gonzalez, “Evidence for a New Variant CYP2D6 Allele CYP2D6J in a Japanese Population Associated with Lower in Vivo Rates of Sparteine Metabolism,” Pharmacogenetics, Vol. 3, No. 5, 1993, pp. 256-263. doi:10.1097/00008571-199310000-00005
M. L. Dahl, Q. Y. Yue, H. K. Roh, I. Johansson, J. Sawe, F. Sjoqvist and L. Bertilsson, “Genetic Analysis of the CYP2D Locus in Relation to Debrisoquine Hydroxylation Capacity in Korean, Japanese and Chinese Subjects,” Pharmacogenetics, Vol. 5, No. 3, 1995, pp. 159-164. doi:10.1097/00008571-199506000-00004
A. Ishiguro, T. Kubota, H. Sasaki, Y. Yamada and T. Iga, “Common Mutant Alleles of CYP2D6 Causing the Defect of CYP2D6 Enzyme Activity in a Japanese Population,” British Journal of Clinical Pharmacology, Vol. 55, No. 4, 2003, pp. 414-415. doi:10.1046/j.1365-2125.2003.01782.x
K. Sakuyama, T. Sasaki, S. Ujiie, K. Obata, M. Mizugaki, M. Ishi-kawa and M. Hiratsuka, “Functional Characterization of 17 CYP2D6 Allelic Variants (CYP2 D6.2, 10, 14A-B, 18, 27, 36, 39, 47-51, 53-55, and 57),” Drug Metabolism and Disposition, Vol. 36, No. 12, 2008, pp. 2460-2467. doi:10.1124/dmd.108.023242
M. Matsunaga, H. Yamazaki, K. Kiyotani, S. Iwano, J. Saruwatari, K. Nakagawa, A. Soyama, S. Ozawa, J. Sawada, E. Kashiyama, M. Kinoshita and T. Kamataki, “Two Novel CYP2D6*10 Haplotypes as Possible Causes of a Poor Metabolic Phe-notype in Japanese,” Drug Metabolism and Disposition, Vol. 37, No. 4, 2009, pp. 699-701. doi:10.1124/dmd.108.026096
I. Johansson, M. Oscarson, Q. Y. Yue, L. Bertilsson, F. Sjoqvist and M. Ingelman-Sundberg, “Genetic Analysis of the Chinese Cy-tochrome P4502D Locus: Characterization of Variant CYP2D6 Genes Present in Subjects with Diminished Ca-pacity for Debrisoquine Hydroxylation,” Molecular Pharmacology, Vol. 46, No. 3, 1994, pp. 452- 459.
T. Tateishi, M. Chida, N. Ariyoshi, Y. Mizorogi, T. Kamataki and S. Kobayashi, “Analysis of the CYP2D6 Gene in Relation to Dextromethorphan O-Demethylation Capacity in a Japanese Population,” Clinical Pharmacology & Therapeutics, Vol. 65, No. 5, 1999, pp. 570-575. doi:10.1016/S0009-9236(99)70077-9
T. Kubota, Y. Yamaura, N. Ohkawa, H. Hara and K. Chiba, “Frequencies of CYP2D6 Mutant Alleles in a Normal Japanese Population and Metabolic Activity of Dextromethorphan O-Demethylation in Different CYP2D6 Genotypes,” British Journal of Clinical Pharmacology, Vol. 50, No. 1, 2000, pp. 31-34. doi:10.1046/j.1365-2125.2000.00209.x
S. H. Gan, R. Ismail, W. A. Wan Adnan and Z. Wan, “Correlation of Tramadol Pharmacokinetics and CYP 2D6*10 Genotype in Malaysian Subjects,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 30, No. 2, 2002, pp. 189-195. doi:10.1016/S0731-7085(02)00214-5
M. Kitahara, K. Kojima, M. Hanada, Y. Kuriyama and A. Ohmura, “Effectiveness of Oral Tramadol Hydrochloride for Chronic Non-Malignant Pain,” Masui, Japanese Journal of Anesthesiology, Vol. 58, No. 8, 2009, pp. 971-975.
G. Wang, H. Zhang, F. He and X. Fang, “Effect of the CYP2D6*10 C188T Polymorphism on Postoperative Tramadol Analgesia in a Chinese Popula-tion,” European Journal of Clinical Pharmacology, Vol. 62, No. 11, 2006, pp. 927-931.doi:10.1007/s00228-006-0191-2
K. Ijichi, K. Nijima, T. Iwagaki, J. Irie and Y. Uratsuji, “A Rando-mized Double-Blind Comparison of Epidural versus Intravenous Tramadol Infusion for Postoperative Analgesia,” Masui, Japanese Journal of Anesthesiology, Vol. 54, No. 6, 2005, pp. 615-621.
Y. Kaneda, I. Kawamura, A. Fujii and T. Ohmori, “Serotonin Syndrome—‘Potential’ Role of the CYP2D6 Genetic Polymorphism in Asians,” International Journal of Neuropsychopharmacology, Vol. 5, No. 1, 2002, pp. 105-106. doi:10.1017/S1461145701002723