Pharmacokinetics and plasma binding of thiopental. I: Studies in surgical XXXX .

@entity1 @entity168
The pharmacokinetics and plasma protein binding of thiopental were investigated in 5 female @entity1 who received a bolus intravenous dose of the drug for induction of anesthesia for gynecologic surgery. Blood samples were collected for 3 to 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 per cent (n equals 10). In healthy volunteers, the plasma protein binding of thiopental was concentration dependent. Percentage bound ranged from 96.7 (n equals 4, @entity168 equals 0.8) at 150 micrograms/ml. Therefore, 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 @entity1 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 @entity1 were as follows: initial distribution volume 13.81 ( @entity168 equals 9.4), apparent volume of distribution 233 1 ( @entity168 equals 98), volume of distribution at steady state 97.51 ( @entity168 equals 40), elimination half-life 11.5 h ( @entity168 equals 1.0) and systemic plasma clearance 0.150 l/min ( @entity168 equals 0.063). None of these parameters correlated with body weight. Values reported by other workers vary from ours and this variation may be explained by the much shorter duration of blood collection used in those studies.
