Transdermal Fentanyl for Cancer Pain Repeated Dose Pharmacokinetics
作者:
Russell Portenoy,
Mary Southam,
Suneel Gupta,
Jeanne Lapin,
Mary Layman,
Charles Inturrisi,
Kathleen Foley,
期刊:
Anesthesiology
(OVID Available online 1993)
卷期:
Volume 78,
issue 1
页码: 36-43
ISSN:0003-3022
年代: 1993
出版商: OVID
关键词: Analgesics, opioid;fentanyl. Anesthetic techniques;transdermal. Pain, chronic;cancer. Pharmacokinetics;transdermal fentanyl
数据来源: OVID
摘要:
BackgroundThe transdermal therapeutic system (fentanyl), or TTS(fentanyl), continuously delivers fentanyl for up to 72 h. The transdermal therapeutic system (fentanyl)-lOO delivers approximately 100 μg/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.MethodsBlood 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).ResultsFor 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.ConclusionsThese 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.
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