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 300mgkg(-1) body weight was administered orally. For maternal blood ethanol concentration, the kinetic equation was: [Formula: see text] 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=0.36). However, the AUC(0-3.5h) 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, h(-1)). The V(max)(EtOH) was 237.6 +/- 71.5 microgml(-1)h(-1) and K(m)(EtOH) was 3.7 +/- 4.7 microgml(-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.
Nava-Ocampo
Alejandro A
AA
The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ont., Canada. navaocampo_aa@yahoo.com
Velázquez-Armenta
Yadira
Y
Brien
James F
JF
Koren
Gideon
G
D000079:Acetaldehyde / Q000097:blood; D000328:Adult; D000465:Algorithms; D000653:Amniotic Fluid / Q000378:metabolism; D019540:Area Under Curve; D002492:Central Nervous System Depressants / Q000097:blood / Q000493:pharmacokinetics*; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D011247:Pregnancy / Q000378:metabolism*
D002492:Central Nervous System Depressants; D000431:Ethanol; D000079:Acetaldehyde