Pharmacokinetics and Plasma Binding of Thiopental. I

Abstract

The pharmacokinetics and plasma protein binding of thiopental were investigated in 5 female patients who received a bolus i.v. dose of the drug for induction of anesthesia for gynecologic surgery. Blood samples were collected for 3-4 days after the dose. Plasma protein binding determinations were also carried out by ultrafiltration and equilibrium dialysis on samples from a panel of healthy volunteers. Plasma concentrations of thiopental were determined by reverse-phase, high-performance liquid chromatography. The coefficient of variation of the method was 2.8% (10). In healthy volunteers, the plasma protein binding of thiopental was concentration dependent. Percentage bound ranged from 96.7 (4, SD = 0.8) at a thiopental concentration of 0.2 .mu.g/ml to 60.4 (5, SD = 0.8) at 150 .mu.g/ml. Saturation of binding sites on rapid administration of the drug may occur, exposing vital organs to unexpectedly high concentrations of free drug. Values of the fraction of thiopental bound in plasma obtained from the surgical patients during the hour following drug administration were similar to values obtained in healthy volunteers at comparable concentrations. Mean pharmacokinetic parameters obtained for thiopental in the surgical patients were as follows: initial distribution volume 13.8 l (SD = 9.4), apparent volume of distribution 233 l (SD = 98), volume of distribution at steady state 97.5 l (SD = 40), elimination half-life 11.5 h (SD = 1.0) and systemic plasma clearance 0.150 l/min (SD = 0.063). None of these parameters correlated with body weight. Values reported by other workers vary, this variation may be explained by the much shorter duration of blood collection used in those studies.