Arterial and Venous Differences of Thiopental Pharmacokinetics as an Intravenous Anesthesia Induction Agent and its Pharmacodynamic Inplication

Kim, Chong Sung; Min, Seong Won; Kim, Hee Soo; Kim, Kwang Woo; Kim, Ho Soon; Shin, Hyun Tae

Abstract

The arterial and venous differences of thiopental. pharmacokinetics and its impact on the onset of pharmacologic effect were examined in 6 male surgical patients with normal renal and hepatic functions during short time period of 6hrs post-intravenous bolus injection over 5 second(5 mg/kg). Arterial and venous blood samples were withdrawn from radial artery and subclavian vein, respectively at the time of right before and after injection(0), 5, 10, 20, 30, 45 (sec), l, 2, 5, 10, 30(min), 1, 2, 3, 4, 5, 6(hrs). Serum concentrations of thiopental were determined by reverse-phase, high performance liquid chromatography and the clinical endpoint of anesthesia induction were interpreted as the time of loss of consciousness by observing spontaneous closing of eyes and loss of eyelash reflex. As the results, significant differences between arterial and venous concentrations were noted during early phase lasting up to 10 minutes. Arterial data was best fitted to tri-exponential decay model. In analysing pharmacokinetic parameters with serum data of 6 hrs duration, there were no significant differences in AUCo-(area under curve), AUCO-t, and clearance(P <0.05), but significant difference in peak concentrations(arterial: 103.97+/-12.15, venons:17.487+/-5.206ug/ml), and times to peak(arterial: 0.67+/-0.037, venous: 1.653+/-0.712min), AUMC O-t, MRT (mean residence time), apparent T 1/2(terminal half-life) and apparent Vdss(steady-state volume of distribution). Spontaneous eye closures were observed within 20 seconds(10-20sec) after the end of injection where arterial concentrations were at peak(n=3) or right after peak(n=3) and otherwise, venous concentrations were at low or even almost at zero(n=3), reflecting the fact that arterial eoncentrations are directly correlated to the clinical efficacy and more important in pharmaco-kinetic and dynamic aspect of drug.