DOSE-RANGING STUDY OF THE OXYTOCIN ANTAGONIST ATOSIBAN IN THE TREATMENT OF PRETERM LABOR

Objective: To evaluate the minimal effective dose regimen of the oxyto cin antagonist atosiban in the treatment of acute preterm labor and th e effect of a bolus on uterine activity within the first 2 hours compa red with no bolus and the same infusion rate. Methods: A randomized, d ouble-blind (except the ritodrine group), parallel group, multicenter study compared four different intravenous atosiban regimens (6.5 mg bo lus plus 300 mu g/minute, placebo bolus plus 300 mu g/minute, 2 mg bol us plus 100 mu g/minute, and 0.6 mg plus 30 mu g/minute) and intraveno us ritodrine with respect to the cessation of uterine contractions for 1 hour or more during infusion, four or fewer contractions per hour i n the last hour of therapy, and discontinuation because of adverse exp eriences. Three hundred two patients were enrolled. Results: The lowes t dose of atosiban (0.6 mg plus 30 mu g/minute) was significantly less effective than ritodrine with respect to cessation of contractions an d four or fewer contractions per hour in the last hour of therapy. Oth er atosiban regimens were comparable to ritodrine, except for the drug discontinuation rate for adverse experiences. Bolus therapy with high -dose atosiban resulted in a significantly greater proportion of patie nts who stopped contracting within the first 2 hours of treatment (17 of 63) compared with those not receiving a bolus (six of 58, P =.017). Because of adverse experiences, the study drug was discontinued in on e of 244 atosiban patients and 15 of 58 ritodrine patients. Conclusion : Atosiban's effect on uterine activity in preterm labor was enhanced by bolus infusion and was similar to the effect of ritodrine, but with fewer side effects.