title: Menses induction in rhesus monkeys using a controlled-release vaginal delivery system containing (15S) 15-methyl prostaglandin F2 alpha methyl ester.
abstract: Polymeric controlled-release vaginal delivery systems were designed for (15S)15-methyl prostaglandin (PG)F2 alpha methyl ester (carboprost methyl). The drug was incorporated into a highly permeable reservoir membrane that was bound to a relatively nonpermeable support membrane. The rate of drug release was controlled by coating the reservoir membrane with a less permeable rate-controlling membrane. Vaginal devices were prepared with in vitro steady-state release rates from 5 to 180 microgram/hour. The release curves were characterized by an initial, transient rapid release of the drug, followed by a linear zero-order release phase. Pregnancy was terminated in rhesus monkeys following a 24-hour treatment with vaginal devices having release rates of carboprost methyl of 45 microgram/hour or greater. Successful menses induction was associated with peripheral plasma concentrations of (15S)15-methyl PGF2 alpha between 2000 and 3000 pg/ml. Peripheral plasma concentrations of progesterone declined very rapidly to less than 1.0 ng/ml in monkeys in which pregnancy was terminated. These studies demonstrate the feasibility of manufacturing controlled-release vaginal delivery systems containing carboprost methyl for use in early pregnancy termination.
mesh_terms: D000028:Abortion, Induced / Q000379:methods* / Q000662:veterinary; D000818:Animals; D002260:Carboprost / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D003692:Delayed-Action Preparations; D005260:Female; D007700:Kinetics; D008598:Menstruation / Q000187:drug effects*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage*; D014621:Vagina
chemical_list: D003692:Delayed-Action Preparations; D011461:Prostaglandins F, Synthetic; D011374:Progesterone; D002260:Carboprost