Varvel J R, Shafer S L, Hwang S S, Coen P A, Stanski D R
Department of Anesthesia, Stanford University School of Medicine, California.
Anesthesiology. 1989 Jun;70(6):928-34. doi: 10.1097/00000542-198906000-00008.
Fentanyl was administered intravenously and transdermally to eight surgical patients to determine the systemic bioavailability and rate of absorption of the transdermally administered drug. Serum fentanyl concentrations reached a plateau approximately 14 h after placement of the transdermal fentanyl delivery system. This plateau was maintained until removal of the system at 24 h. The decline in serum fentanyl concentrations after removal of the transdermal system had a terminal half-life of 17.0 +/- 2.3 h (mean +/- SD), considerably longer than the terminal elimination half-life seen after intravenous administration of fentanyl in the same patients (6.1 +/- 2.0 h). The rate of fentanyl absorption, predicted to be 100 micrograms/h from in vitro data, appeared to be relatively constant during a period starting 4-8 h after placement of the transdermal system until removal of the system at 24 h. The rate of absorption during this period was 91.7 +/- 25.7 micrograms/h. After removal of the transdermal fentanyl delivery system, absorption continued at a declining rate. This indicates that the long terminal half-life of serum fentanyl concentrations after transdermal system removal is due to continued slow absorption of fentanyl, probably from a cutaneous depot of drug at the site of prior transdermal system placement. At the time of removal of the transdermal fentanyl system, 1.07 +/- 0.43 mg of drug remained in this depot. Systemic fentanyl bioavailability was found to be 0.92 +/- 0.33, with no evidence of significant cutaneous metabolism or degradation by the skin's bacterial flora. The transdermal administration of fentanyl produces relatively constant serum fentanyl concentrations for significant periods of time in the postsurgical patient requiring analgesic therapy.
对8名外科手术患者静脉注射和经皮给予芬太尼，以确定经皮给药的全身生物利用度和吸收速率。在放置经皮芬太尼给药系统后约14小时，血清芬太尼浓度达到平台期。该平台期一直维持到24小时移除该系统。移除经皮系统后血清芬太尼浓度的下降，其终末半衰期为17.0±2.3小时（平均值±标准差），明显长于同一患者静脉注射芬太尼后的终末消除半衰期（6.1±2.0小时）。根据体外数据预测，芬太尼的吸收速率为100微克/小时，在放置经皮系统后4 - 8小时开始至24小时移除该系统期间，吸收速率似乎相对恒定。在此期间的吸收速率为91.7±25.7微克/小时。移除经皮芬太尼给药系统后，吸收仍以递减速率继续。这表明移除经皮系统后血清芬太尼浓度的长终末半衰期是由于芬太尼持续缓慢吸收，可能来自先前经皮系统放置部位的皮肤药物储库。在移除经皮芬太尼系统时，该储库中仍残留1.07±0.43毫克药物。发现芬太尼的全身生物利用度为0.92±0.33，没有证据表明皮肤有明显的代谢或被皮肤细菌菌群降解。对于需要镇痛治疗的术后患者，经皮给予芬太尼在相当长的时间内可产生相对恒定的血清芬太尼浓度。
