title: Population pharmacokinetics of transdermal fentanyl in patients with cancer-related pain.
abstract: Determining the appropriate dose of transdermal fentanyl (TDF) for the alleviation of cancer pain requires determining the factors causing variations in serum fentanyl concentration after TDF treatment. The objective of this study was to identify these factors and incorporate them into a formula that can be used to predict serum fentanyl concentration after application of a TDF patch. Blood samples of cancer patients treated with a TDF patch for the alleviation of pain were collected at 24, 48, and 72 hours after application to evaluate population pharmacokinetics using the nonlinear mixed-effect model (NONMEM). Based upon this evaluation, Child-Pugh Score and use of a cytochrome P450 3A4 (CYP3A4) inducer were identified as the most significant factors in variations in serum fentanyl concentration and incorporated into the following Final Model formula: CL(fenta) (L/h) = 3.53 × (15 - Child-Pugh Score) × (1 + 1.38 × use or no use of CYP3A4 inducer). Bootstrap evaluation of the Final Model revealed a high convergence rate, suggesting that the model formula is a reliable and useful tool for determining TDF dose for the alleviation of cancer pain.
authors: Department of Pharmacy, Kitasato University Hospital, Minami-ku, Kanagawa, Japan. kokubun@kitasato-u.ac.jp
authors: Hideya
authors: H
authors: Kokubun
authors: Keiichi
authors: K
authors: Ebinuma
authors: Motohiro
authors: M
authors: Matoba
authors: Risa
authors: R
authors: Takayanagi
authors: Yasuhiko
authors: Y
authors: Yamada
authors: Kazuo
authors: K
authors: Yago
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000150:complications*; D017711:Nonlinear Dynamics; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D057968:Transdermal Patch
chemical_list: D000701:Analgesics, Opioid; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D005283:Fentanyl