title: Population pharmacokinetics of oxycodone in patients with cancer-related pain.
abstract: Oxycodone is an opioid widely prescribed to cancer patients for pain relief. However, the pharmacokinetics of oxycodone has not been sufficiently examined. Therefore the aim of this work was to study population pharmacokinetics of oxycodone in patients with cancer pain. The authors analyzed 108 serum oxycodone samples of 33 individuals with nonlinear mixed-effects model (NONMEM). Population pharmacokinetics was calculated using the one-compartment model of clearance, volume of distribution, bioavailability, absorption constant rate, and lag time. An exponential error model was used to determine interindividual variability and a relative error model was applied to assess residual variability. Population pharmacokinetics of oxycodone at the end point were as follows: CL(L/h) = 10.7 × [1 + (2 - Child-Pugh Classification)] (Class: A = 0, B = 1, C = 2); V(d) (L) = 193; k(a) (h(-1)) = 0.336; T(lag) (h) = 0.859; F (%) = 63.9. Interindividual variability was CL: 30.5%, V(d): 44.6%, and F: 37.0%, and residual variability was 16.2%. As the total clearance in patients with liver dysfunction (Child-Pugh class B) was reduced to 33.3%, serum concentration of oxycodone increased by 1.5. Therefore, it became clear that dose adjustments are essential when treating patients with liver dysfunction. These findings suggest that population parameters are useful for evaluating pharmacokinetics of oxycodone in patients with cancer pain.
authors.affiliation: Department of Pharmacy, Kitasato University Hospital, Kanagawa, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Komatsu
authors.forename: Hideya
authors.initials: H
authors.lastname: Kokubun
authors.forename: Ai
authors.initials: A
authors.lastname: Suzuki
authors.forename: Risa
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Motohiro
authors.initials: M
authors.lastname: Matoba
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yago
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000503:physiopathology; D017711:Nonlinear Dynamics; D010098:Oxycodone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D014018:Tissue Distribution
chemical_list: D000701:Analgesics, Opioid; D010098:Oxycodone