title: Transdermal fentanyl for cancer pain. Repeated dose pharmacokinetics.
abstract: BACKGROUND
  The transdermal therapeutic system (fentanyl), or TTS(fentanyl), continuously delivers fentanyl for up to 72 h. The transdermal therapeutic system (fentanyl)-100 delivers approximately 100 micrograms/h. The repeated dose pharmacokinetics of this drug using the recommended dosing interval have not been evaluated previously and were determined in the present study.
  
  
  METHODS
  Blood samples were obtained from ten opioid-tolerant cancer patients who received five applications of TTS(fentanyl) at 72-h intervals. A sample of venous blood was taken before each dose; multiple samples were taken during and after the fifth application. A gas chromatographic/mass spectrometry method was used to assay fentanyl (limit of detection 0.2 ng/ml).
  
  
  RESULTS
  For the fifth dose, the mean (SD) maximum concentration was 2.6 (1.3) ng/ml and the mean (SD) area under the serum fentanyl concentration-time curve (0-72 h) was 116.9 (59.9). Following removal of the system, the mean (SD) apparent half-life was 21.9 (8.9) h. There were no differences among the serum fentanyl concentrations measured before the second through fifth doses. Fentanyl absorption was 47% complete at 24 h, 88% complete at 48 h, and 94% complete at 72 h. The mean (SD) dose delivered during the 72-h period was 4.3 (1.1) mg. A first-dose trough concentration predicted from fifth-dose kinetics and the actual first-dose trough concentration were very similar. Adverse effects ascribed to the transdermal system were minimal.
  
  
  CONCLUSIONS
  These results suggest that steady-state serum concentrations are approached by the second dose of TTS(fentanyl) and that the kinetics are stable with repeated dosing. The apparent half-life following system removal is relatively long, indicating ongoing absorption from a subcutaneous depot.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
authors.forename: R K
authors.initials: RK
authors.lastname: Portenoy
authors.forename: M A
authors.initials: MA
authors.lastname: Southam
authors.forename: S K
authors.initials: SK
authors.lastname: Gupta
authors.forename: J
authors.initials: J
authors.lastname: Lapin
authors.forename: M
authors.initials: M
authors.lastname: Layman
authors.forename: C E
authors.initials: CE
authors.lastname: Inturrisi
authors.forename: K M
authors.initials: KM
authors.lastname: Foley
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000503:physiopathology; D003110:Colonic Neoplasms / Q000503:physiopathology; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology
chemical_list: D005283:Fentanyl