Pharmacokinetics and Plasma Binding of Thiopental. II

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Abstract
The effect of pregnancy on the disposition of thiopental was studied. The major factors which influence the placental transfer of the drug to the fetus were determined. Maternal venous (MV) and umbilical venous (UV) and arterial (UA) blood samples were collected at delivery from 11 pregnant women at term who received thiopental for induction of anesthesia for elective cesarian section. A detailed study of the pharmacokinetics of thiopental was carried out in 7 of these subjects and blood samples were collected for 80-100 h following thiopental administration. A transient rise in thiopental plasma concentration was observed at delivery. Mean values of pharmacokinetic parameters (.+-. SD) were: initial distribution volume (V1) 17.3 l (.+-. 8.5), apparent volume of distribution (Vd.beta.) 564 l (.+-. 343), volume of distribution at steady state (Vss) 288 l (.+-. 180), systemic plasma clearance (Clp) 0.286 l/min (.+-. 0.156), rate of change of volume of distribution at 0 time (RVdo) 1.03 l/min (.+-. 0.36) and elimiantion half-life (t1/2) 26.1 h (.+-. 12.6). Comparison of these data with previously reported data in nonpregnant surgical patients shows that Vd.beta., Vss and t1/2 are significantly greater at cesarean section (P < 0.05) and that systemic plasma clearance shows a similar trend. UA and UV values at delivery were similar within individuals. There was no correlation between the ratio UV/MV at delivery and the dosing-delivery interval (.DELTA.t), or between UV and the administered dose or .DELTA.t. There were good correlations between UV (corrected for dose) and the reciprocals of V1, Vd.beta., Vss and plasma clearance of thiopental. This demonstrates that differences in maternal distribution and elimination characteristics of thiopental may be more important determinants of intersubject differences in fetal drug exposure than differences in dose or .DELTA.t.

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