Pharmacokinetic and Hemodynamic Effects of Caffeine in the Pregnant Sheep

Caffeine citrate in doses of 6.96 mg/kg (equivalent to 3.50 mg/kg of caffeine) of combined maternal and fetal weight and 69.6 mg/kg (35.0 mg/kg of caffeine) was administered in 1-dl solutions intravenously over ten minutes to chronically prepared pregnant sheep. The ewes and their fetuses were monitored for cardiovascular and acid-base status. The mean maternal and fetal caffeine concentrations were simultaneously evaluated with a two-compartment pharmacokinetic model. Fetal concentrations in excess of 80% of maternal concentrations were rapidly achieved and maintained. Caffeine was undetectable in all the maternal and fetal samples obtained 48 hours after the infusion. Both doses caused similar but slight reductions in uterine blood flow without adversely affecting fetal and maternal acid-base status. Only the higher concentration of the drug produced a significant maternal and fetal tachycardia. The high fetal concentrations of caffeine were believed to be responsible for the persistent fetal tachycardia.