title: [Interindividual variation of pharmacokinetic disposition of and clinical responses to opioid analgesics in cancer pain patients].
abstract: Use of prescription opioids for cancer pain according to the World Health Organization analgesic ladder has been accepted in Japan. Although oxycodone and fentanyl are commonly used as first-line analgesics, a few clinical reports have been published on interindividual variations in their pharmacokinetics and clinical responses in cancer patients. (1) Some factors relating to CYP2D6, CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu 1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans. The relations between their genetic variations and clinical responses to oxycodone are being revealed in limited groups. In our study, the impact of genetic variants and pharmacokinetics on clinical responses to oxycodone were evaluated in Japanese populations. (2) Opioid switching improves the opioid tolerance related to the balance between analgesia and adverse effects. Some patients have difficulty in obtaining better opioid tolerance in recommended conversion ratios. The activities of CYP3A, ABCB1, and OPRM1 contribute to the interindividual variations in clinical responses to fentanyl in cancer patients. However, the variations in opioid switching remain to be clarified in clinical settings. In our study, genetic factors related to interindividual variations in clinical responses in opioid switching to fentanyl were revealed in Japanese populations. In this symposium review, the possibility of approaches to personalized palliative care using opioids based on genetic variants of CYP2D6, CYP3A5, ABCB1, and OPRM1 is discussed.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D057915:Drug Substitution; D004361:Drug Tolerance / Q000235:genetics; D005283:Fentanyl / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D014644:Genetic Variation; D006801:Humans; D009369:Neoplasms / Q000150:complications*; D010098:Oxycodone / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D010148:Intractable Pain / Q000188:drug therapy* / Q000235:genetics*; D010166:Palliative Care; D010597:Pharmacogenetics; D057285:Precision Medicine
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000701:Analgesics, Opioid; D010098:Oxycodone; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D005283:Fentanyl