芬太尼在马体内静脉注射和经皮给药后的药代动力学

Maxwell L K, Thomasy S M, Slovis N, Kollias-Baker C

K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, California 95616, USA.

Equine Vet J. 2003 Jul;35(5):484-90. doi: 10.2746/042516403775600415.

REASONS FOR PERFORMING STUDY

Although fentanyl has been reported to cause CNS excitation in horses, a transdermal therapeutic system (TTS) containing this mu agonist has recently been used empirically in equine medicine to treat moderate to severe pain. A better understanding of the disposition of fentanyl following transdermal administration would facilitate the clinical use of TTS fentanyl to obtain analgesia in horses.

OBJECTIVES

To determine the pharmacokinetics of fentanyl following i.v. and TTS patch administration in healthy, mature horses and to evaluate the tolerance of horses to TTS fentanyl administration.

METHODS

The pharmacokinetics of fentanyl in serum were assessed following a single i.v. dose, a single TTS dose, and multiple TTS doses in 6 healthy horses. Physical examinations, haematology and serum biochemistry analyses during transdermal fentanyl application were then performed to determine tolerance of continuous fentanyl administration.

RESULTS

Fentanyl was very rapidly and completely absorbed following a single TTS dose. Mean serum fentanyl concentrations consistent with analgesia in other species were reached by 1 h and maintained until 32 h after patch application. Similar steady state serum concentrations were obtained when multiple doses of TTS fentanyl were administered every 48 or 72 h over 8 or 9 days, with less fluctuation in serum concentrations during the 48 h dosing interval. Three horses exhibited brief (< 12 h) episodes of increased body temperature; however, transdermal fentanyl administrations were not associated with other significant changes in haematology and biochemistry panels or physical examination findings.

CONCLUSIONS AND POTENTIAL RELEVANCE

Although the pharmacodynamics of fentanyl have not been investigated fully in horses, transdermally-administered fentanyl exhibited a favourable pharmacokinetic profile without clinically relevant side effects and may be a useful analgesic in equine patients.

开展本研究的原因

尽管据报道芬太尼可引起马的中枢神经系统兴奋，但一种含有这种μ激动剂的透皮治疗系统（TTS）最近已在马医学中凭经验用于治疗中度至重度疼痛。更好地了解芬太尼经皮给药后的处置情况将有助于TTS芬太尼在马身上的临床应用以获得镇痛效果。

目的

确定在健康、成熟的马静脉注射和经TTS贴片给药后芬太尼的药代动力学，并评估马对TTS芬太尼给药的耐受性。

方法

在6匹健康马中，评估单次静脉注射剂量、单次TTS剂量和多次TTS剂量后血清中芬太尼的药代动力学。然后在经皮应用芬太尼期间进行体格检查、血液学和血清生化分析，以确定连续芬太尼给药的耐受性。

结果

单次TTS剂量后，芬太尼吸收非常迅速且完全。在贴片应用后1小时达到与其他物种镇痛效果一致的平均血清芬太尼浓度，并维持至32小时。当在超过8或9天的时间内每48或72小时给予多次TTS芬太尼剂量时，可获得相似的稳态血清浓度，且在48小时给药间隔期间血清浓度波动较小。3匹马出现短暂（<12小时）体温升高；然而，经皮给予芬太尼与血液学和生化指标或体格检查结果的其他显著变化无关。