The effect of caffeine ingestion on pharmacokinetics of caffeine and its metabolites after a single administration in pregnant rats.

Abstract

The pharmacokinetics of caffeine and its metabolites were studied in pregnant rats in order to clarify the effects of maternal caffeine ingestion on the caffeine disposition. On gestational day 18 the single intravenous or oral 10 mg/kg dose of caffeine was administered to pregnant rats who had received drinking water containing 0.04% caffeine or water ad lib during the premating and/or pregnant periods. Concentrations of caffeine and its dimethylxanthines were simultaneously determined by high-performance liquid chromatography. The caffeine plasma concentration-time curves were analyzed by assumption of a one-compartment model. The apparent volume of distribution of caffeine in rats given caffeine only during pregnancy was decreased. The elimination rate constant (kel) of caffeine in most of the rats taking caffeine during pregnancy was increased. The rats which had received caffeine throughout the premating and pregnant periods had a relatively high total body plasma clearance (CL) of caffeine. The kel and the CL widely varied in the rats taking caffeine during pregnancy. The individual values of kel or CL in pregnant rats were significantly correlated with the molar concentration ratios of the metabolites to caffeine in plasma at 8 h after administration of caffeine. It is concluded that the caffeine disposition is influenced by the different modes of maternal caffeine ingestion during the premating and/or pregnant periods.