Pharmacokinetics and Plasma Binding of Thiopental. II: Studies at Cesarean Section


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Abstract

This study was undertaken to investigate the effect of pregnancy on the disposition of thiopental and to determine the major factors which influence the placental transfer of the drug to the fetus. 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 to 100 hours 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 1 (±8.5), apparent volume of distribution (V***β) 564 1 (±343), volume of distribution at steady state (Vss) 288 1 (±180), systemic plasma clearance (Clp) 0.286 1/min (±0.156), rate of change of volume of distribution at zero time (RVd0) 1.03 1/min (±0.36) and elimination half-life (t1/2) 26.1 h (±12.6). Comparison of these data with our previously reported data in nonpregnant surgical patients shows that V, Vss, and T1/2 are significantly greater at cesarian 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 (δt), or between UV and the administered dose or δt. There were good correlations between UV (corrected for dose) and the reciprocals of V1, V, 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 δt.

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