THE PHARMACOKINETICS OF THE OXYTOCIN ANTAGONIST ATOSIBAN IN PREGNANT-WOMEN WITH PRETERM UTERINE CONTRACTIONS

OBJECTIVE: Our purpose was to evaluate the pharmacokinetics of atosiba n, an oxytocin antagonist, during and after intravenous infusion in pr egnant patients having at least six contractions per hour. The relatio nship between atosiban infusion and uterine activity was also assessed . STUDY DESIGN: Plasma samples from eight pregnant patients treated wi th intravenous atosiban (300 mu g/min far 6 to 12 hours) were analyzed for atosiban concentration by a specific radioimmunoassay procedure. Contraction rate data were obtained by external tocodynamometry for 1 hour before the infusion and during the subsequent infusion. RESULTS: The average steady-state plasma concentrations of patients receiving i ntravenous atosiban were 442 +/- 73 ng/ml (mean +/- SD), with steady s tate achieved by 1 hour after the start of the infusion. After the com pletion of the infusion, plasma concentrations declined rapidly in a b iexponential manner with initial and terminal half-life estimates of 1 3 +/- 3 and 102 +/- 18 minutes, respectively. The effective half-life was 18 +/- 3 minutes. The plasma clearance of atosiban was relatively high (42 L/hr) and the volume of distribution (approximately 18 L) was consistent with distribution into extracellular fluid. Of the seven p atients evaluated for uterine activity, the mean contraction rate decr eased by 75% during the third hour of treatment and remained low until treatment termination. CONCLUSION: On the basis of earlier published reports, the pharmacokinetics of atosiban in pregnant patients are sim ilar to those in nonpregnant women. Although the patient population wa s small, a consistent reduction in uterine activity was observed durin g atosiban infusion.