The disposition and placental transfer of diazepam in cesarean section

The disposition parameters and placental transfer of diazepam were determined from blood and both plasma total and free concentration data in five women who had not undergone labor and who received diazepam (5 mg intravenously for 2 minutes) 1 1 2 to 3 hours before cesarean section at term. All patients exhibited smooth log plasma free concentration-time profiles. In contrast, marked increases in plasma total (approximate 50% increase) and blood (approximate 40% increase) diazepam concentrations occurred at delivery. The plasma total and blood concentration fluctuations were associated with reciprocal variations in diazepam percent free in plasma. For each patient there was a substantial increase in plasma nonesterified fatty acid (NEFA) concentration during the surgical period. There was a significant correlation (p < 0.02) between diazepam percent free and plasma NEFA concentration on the day of delivery, suggesting that the fluctuations in percent free, and hence plasma total and blood diazepam concentrations, were mediated in part by variations in plasma NEFA concentration. Disposition parameters were calculated for four of the patients; the mean free plasma clearance of diazepam was 42.5 ml/min/kg, similar to the mean value reported previously for nonpregnant women of comparable age. For each mother-infant pair at delivery the ratio of total plasma diazepam concentration in umbilical vein plasma to that in maternal vein plasma was considerably greater than unity (mean ± SD = 1.73 ± 0.47), whereas the corresponding ratio for free plasma diazepam concentration was near unity (0.92 ± 0.09). The apparent accumulation of diazepam in the fetal circulation, based on total plasma concentrations, was the result of more extensive plasma binding in umbilical plasma compared with maternal plasma (diazepam percent free of 1.52 ± 0.39 and 2.88 ± 1.05, respectively).