猪丙泊酚微乳和长链脂肪乳的血栓弹力描记和药代动力学特征。

Thromboelastographic and pharmacokinetic profiles of micro- and macro-emulsions of propofol in swine.

机构信息

Department of Anesthesiology, University of Florida, Gainesville, 32610-0254, USA.

出版信息

Biopharm Drug Dispos. 2010 Jul;31(5-6):269-77. doi: 10.1002/bdd.709.

DOI:10.1002/bdd.709

PMID:20578214

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3021748/

Abstract

PURPOSE

Compared with traditional macroemulsion propofol formulations currently in clinical use, microemulsion formulations of this common intravenous anesthetic may offer advantages. The pharmacokinetics and coagulation effects as assessed by thromboelastography of these formulations were characterized in swine.

METHODS

Yorkshire swine (20-30 kg, either sex, n=15) were sedated, anesthetized with isoflurane, and instrumented to obtain a tracheostomy, internal jugular access and carotid artery catheterization. Propofol (2 mg/kg, 30 s) was administered as a macroemulsion (10 mg/ml; Diprivan; n=7) or a custom (2 mg/kg, 30 s) microemulsion (10 mg/ml; n=8). Arterial blood specimens acquired pre- and post-injection (1 and 45 min) were used for thromboelastography. Arterial blood specimens (n=12 samples/subject, 60 min) were serially collected, centrifuged and analysed with solid-phase extraction with UPLC to determine propofol plasma concentrations. Non-compartmental pharmacokinetic analysis was applied to plasma concentrations.

RESULTS

No changes were noted in the thromboelastographic R time (p=0.74), K time (p=0.41), alpha angle (p=0.97), or maximal amplitude (p=0.71) for either propofol preparation. Pharmacokinetic parameters k (p=0.45), t(1/2) (p=0.26), C(o) (p=0.89), AUC(0-infinity) (p=0.23), CL (p=0.14), MRT (p=0.47), V(ss) (p=0.11) of the two formulations were not significantly different.

CONCLUSION

The microemulsion and macroemulsion propofol formulations had similar pharmacokinetics and did not modify thromboelastographic parameters in swine.

摘要

目的

与目前临床使用的传统丙泊酚乳剂制剂相比，该常用静脉麻醉剂的微乳剂制剂可能具有优势。本研究通过血栓弹力描记法评估了这些制剂的药代动力学和凝血效应，并在猪模型中进行了研究。

方法

20-30kg 的约克夏猪（雌雄各半，n=15）给予镇静，异氟烷麻醉，行气管切开术、颈内静脉置管和颈动脉导管置管。猪接受丙泊酚（2mg/kg，30s）乳剂（10mg/ml；Diprivan；n=7）或定制（2mg/kg，30s）微乳剂（10mg/ml；n=8）注射。注射前（1 分钟）和注射后（45 分钟）采集动脉血标本进行血栓弹力描记。取动脉血标本（n=12 个样本/只，60 分钟），采用固相萃取-超高效液相色谱法进行分析，以确定丙泊酚的血浆浓度。采用非房室药代动力学分析丙泊酚的血浆浓度。

结果

两种丙泊酚制剂均未改变血栓弹力描记 R 时间（p=0.74）、K 时间（p=0.41）、α角（p=0.97）或最大振幅（p=0.71）。两种制剂的药代动力学参数 k（p=0.45）、t(1/2)（p=0.26）、C(o)（p=0.89）、AUC(0-infinity)（p=0.23）、CL（p=0.14）、MRT（p=0.47）、V(ss)（p=0.11）均无显著差异。