title: Impact of CYP3A5 and ABCB1 gene polymorphisms on fentanyl pharmacokinetics and clinical responses in cancer patients undergoing conversion to a transdermal system.
abstract: The aim of this study was to evaluate the influence of CYP3A5 and ABCB1 gene polymorphisms on fentanyl pharmacokinetics and clinical responses in cancer patients undergoing conversion to a transdermal system. Sixty Japanese cancer patients being treated with a fentanyl transdermal reservoir system according to the current Japanese guidelines were enrolled. Blood samples were obtained 192 h after conversion to the fentanyl transdermal system. Clinical responses after fentanyl application were evaluated by determining the incidences of adverse effects and rescue medication. The plasma concentration of fentanyl normalized with the measured absorption rate was significantly higher in the CYP3A5*3/*3 group than in the *1/*1 and *1/*3 groups (p = 0.048 and 0.021, respectively). Greater incidences of central adverse effects were observed in CYP3A5*3/*3 patients than in *1/*1+*1/*3 patients (odds ratio [OR], 3.49; 95% confidence interval [95% CI], 1.13-10.75; p = 0.029). Fewer patients with the ABCB1 1236TT allele than the 1236C allele needed rescue medication (OR, 0.17; 95% CI, 0.03-0.89; p = 0.036). CYP3A5*3 affected the pharmacokinetics of fentanyl and increased the incidence of central adverse effects. ABCB1 1236TT was associated with decreased administration of rescue medication after switching to the transdermal fentanyl system. In conclusion, these gene polymorphisms may predict clinical responses to fentanyl in cancer patients being converted to the transdermal system.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takashina
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Mino
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yagi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000279:Administration, Cutaneous; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D016903:Drug Monitoring; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005838:Genotype; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D016017:Odds Ratio; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D005283:Fentanyl