Elimination kinetics of ethanol in pregnant women

To evaluate the pharmacokinetics of ethanol in the early second trimester of pregnancy, ethanol concentrations simultaneously measured in the maternal blood (EtOH-MB) and in the amniotic fluid (EtOH-AF) of six pregnant women were obtained from a previous study in which a single ethanol dose of 300 mg kg ^-1 body weight was administered orally. For maternal blood ethanol concentration, the kinetic equation was: dC_EtOH-MBdt=-k ₁₂+V_maxEtOHK_mEtOH+C _EtOH-MB×C_EtOH-MB+(k₂₁×C _EtOH-AF) where k₁₂ and k₂₁ are, respectively, the rate constant of ethanol transfer from either the central compartment to the peripheral compartment or vice versa; V_maxEtOH is the maximal velocity for ethanol oxidation; and K_mEtOH is the concentration at which half of the maximal rate of ethanol elimination is reached. The maximum concentration of EtOH in AF was 60% lower than in MB (P=0.036). However, the AUC_{0-3.5 h} in AF was only 16% lower than the value for MB (P=0.059). The k₁₂ (0.20±0.26 h^-1) was almost twice faster than k₂₁ (0.13±0.20 h^-1). The V_maxEtOH was 237.6±71.5 μg ml^-1 h^-1 and K_mEtOH was 3.7±4.7 μg ml^-1. Our results imply that in the early second trimester, ethanol metabolism is fast. However, ethanol clearance from the AF is slower than ethanol clearance in MB. This process is widely variable, and our findings may partially explain the wide variability of ethanol's toxic effects on the fetus.