Effect of pregnancy on ritodrine pharmacokinetics

Abstract

Dosing regimens for ritodrine are based in large part on pharmacokinetic studies performed with nonpregnant subjects. Pregnancy is characterized by changes in renal blood flow, plasma volume, protein concentration, and hepatic function. These physiologic changes frequently alter drug pharmacokinetics. To define the effect of pregnancy on ritodrine kinetics, we compared ritodrine pharmacokinetics in four pregnant and four nonpregnant rhesus monkeys. Significant differences were demonstrated in the distribution phase half-life (0.40 +/- 0.08 hours in the pregnant monkeys and 0.21 +/- 0.03 hours in the nonpregnant animals), volume of distribution (1.99 +/- 0.94 L/kg in the pregnant monkeys and 4.75 +/- 0.90 L/kg in the nonpregnant animals), plasma clearance (18.8 +/- 7.1 ml/min/kg in the pregnant monkeys and 27.2 +/- 5.0 ml/min/kg in the nonpregnant animals), and disposition half-life (1.8 +/- 0.4 hours in the pregnant monkeys and 3.3 +/- 0.4 hours in the nonpregnant animals). Pregnant animals receiving ritodrine had higher steady-state plasma concentrations than nonpregnant animals (104 versus 53 ng/ml at an infusion rate of 2 micrograms/kg/min). These data indicate that dosing regimens for ritodrine based on studies of nonpregnant subjects may be subject to considerable error.