Clinical comparison of abortifacient activity of vaginally administered prostaglandin E2 in two dosage forms

Abstract

The effect of prostaglandin E2 (PGE2) release rate from an intravaginal suppository on induced abortion was investigated in a randomized, double-blind study of 71 women who were 7-22 weeks pregnant. 2 dosage forms were compared. Base A was selected to provide a more hydrophilic character than base B. 6 vaginal suppositories, inserted at 4-8 hour intervals as deemed necessary for the clinical progress of abortion, were available for each patient. If abortion did not occur within 48 hours, the trial was discontinued. When time for 50% dissolution of PGE2 (t50%) was plotted as a function of pH for the 2 suppository formulations, the curve for base A was sigmoidal in shape, showing a more rapid release of PGE2 and pH increase. In contrast, base B demonstrated a t50% value of 30 hours which was independent of pH. This independence suggested the hypothesis that the clinical performance of base B would be more uniform than a base A formulation and would exhibit a longer duration of biologic action. Use of base A was found to produce a slight increase in the frequency of successful abortions (79% with base A versus 70.3% with base B). There were no significant differences in the mean times from treatment initiation to complete abortion, the number of incomplete abortions, or failure to abort between the 2 study groups. There was a nonsignificant trend toward reduced total drug use in the base A group. Examination of side effects indicated that women receiving PGE2 in base B had a greater but nonsignificant tendency to experience nausea (62.2% in group B, 58.8% in group A) and vomiting (83.8% group B, 76.5% group A); however, there was a significantly greater amount of diarrhea in the base B group (70.3%) than in the base A group (41.2%). It was concluded that there are no major differences in abortifacient efficiency or the general incidence of side effects when PGE2 therapy in 2 dosage forms is compared. However, a more hydrophilic base, which exhibits a more rapid release of PGE2, appears to slightly reduce side effects and efficacy.