The effect of pregnancy on the pharmacokinetics of caffeine

Caffeine is eliminated mainly by metabolism to demethylated and oxidised derivatives. High individual variability is therefore expected from variations and changes in the capability of the organism to metabolize xenobiotics. An increase of the half-life of elimination of caffeine has been reported during the final weeks of pregnancy. In this study, the half-lifes of caffeine were determined by HPLC-analysis of samples of saliva in male and non-pregnant females and in women during pregnancy and after parturition. The half-life of caffeine increases from an average of 3 h for non-pregnant women to 10.5 h during the last 4 weeks of pregnancy. This increase is already occurring during the first part of pregnancy. The individual values could not be correlated with age, weight, consumption of coffee or smoking habits. An increase of the apparent volume of distribution can also be ruled out as an explanation for the marked increase of the half-life. The main effect of a prolonged half-life is the accumulation of caffeine in the body, unless the consumption is reduced appropriately. Thus, the greatly increased half-life of caffeine during pregnancy could produce adverse effects at a consumption which although considered as high is not excessive under normal conditions. This possibly explains the observation that heavy coffee drinking during pregnancy is linked to a low birthweight in the neonate. Due to the non-specificity of some of the symptoms of caffeine toxicity, pregnant women with such symptoms might be unable to trace the reason for their discomfort if they are not instructed by their physician about the higher susceptibility to caffeine during pregnancy.