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Thromboelastographic and pharmacokinetic profiles of micro‐ and macro‐emulsions of propofol in swine

2010; Wiley; Volume: 31; Issue: 5-6 Linguagem: Inglês

10.1002/bdd.709

1099-081X

Timothy E. Morey, Jerome H. Modell, Jorge Esparteiro Garcia, Michael Bewernitz, Hartmut Derendorf, Manoj Varshney, Nikolaus Gravenstein, Dinesh O. Shah, Donn M. Dennis,

Anesthesia and Sedative Agents

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