Hexoprenaline pharmacokinetics in pregnant and nonpregnant sheep

Hexoprenaline, a beta 2-sympathomimetic agent, is used to suppress uterine contractions in the treatment of premature labor. However, little is known regarding the potential of this drug to undergo placental transfer or whether the pregnant state alters any of the pharmacokinetic parameters. Using sheep as a model, intravenous doses of 14C-hexoprenaline were administered to pregnant and non-pregnant animals. Measurable levels of radioactivity did not appear in fetal blood samples. After intravenous bolus administration, blood concentrations in the ewe could be fitted by a triexponential curve characteristic of a three-compartment pharmacokinetic model. Following intravenous infusion, a biexponential curve described the decline in blood concentrations. Mean terminal half lives for total radioactivity ranged from 2.5 to 4.2 hours. The pregnant animals tended to exhibit smaller apparent volumes of distribution and lower values for total body clearance, normalized to body weight, compared to non-pregnant sheep.