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.
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 cancerpatients 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: R Rolke; S Rolke; S Hiddemann; M Mücke; H Cuhls; L Radbruch; F Elsner; V Peuckmann-Post Journal: Internist (Berl) Date: 2016-10 Impact factor: 0.743
Authors: Carla Ripamonti; Elena Fagnoni; Tiziana Campa; Cinzia Brunelli; Franco De Conno Journal: Support Care Cancer Date: 2006-02-17 Impact factor: 3.603