Elimination kinetics of ethanol in pregnant women
Abstract
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- MB dt =‑ k 12+ V max EtOH K m EtOH +C EtOH- MB ×C EtOH- MB +(k 21×C EtOH- AF ) where k 12 and k 21 are, respectively, the rate constant of ethanol transfer from either the central compartment to the peripheral compartment or vice versa; V max EtOH is the maximal velocity for ethanol oxidation; and K m EtOH 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 k 12 (0.20±0.26 h ‑1) was almost twice faster than k 21 (0.13±0.20 h ‑1). The V max EtOH was 237.6±71.5 μg ml ‑1 h ‑1 and K m EtOH 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.
- Publication:
-
Reproductive Toxicology
- Pub Date:
- January 2004
- DOI:
- 10.1016/j.reprotox.2004.02.012
- Bibcode:
- 2004RepTx..18..613N
- Keywords:
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- Ethanol pharmacokinetics;
- Theoretical models;
- Transplacental exposure