Phenobarbital Pharmacokinetics and Salivary and Serum Concentrations in Pregnancy

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Abstract
The pharmacokinetics and the ratio between salivary and serum concentrations of phenobarbital (PB) were determined in 10 women undergoing treatment in late pregnancy. An .apprx. 2.5-fold variation was measured in the apparent relative clearance rates of PB in the women studied. The means of the total clearance rate (0.255 l/h), the relative clearance rate (4.0 ml/h per kg body wt), the elimination half-life (95 h), the elimination rate constant (0.0071/h) and the apparent volume of distribution (35.49 l) were within the ranges observed in nonpregnant subjects. The PB concentration in saliva was 34% of that in serum. Salivary and serum levels of PB correlated closely with each other. Serum .gamma.-glutamyl transpeptidase activity increased and total bilirubin concentrations decreased during PB treatment, both of which can be linked to the PB-caused hepatic microsomal enzyme induction phenomenon. The variation in clearance rate emphasized the importance of close monitoring of PB treatment of pregnant women. Salivary PB measurements evidently can be used with sufficient accuracy to predict PB concentrations in the serum and to optimize PB treatment during pregnancy.