BACKGROUND: It has been shown that the route of administration of misoprostol has a strong impact on the pharmacokinetic profile and result in different clinical efficacy. No study has so far evaluated the pharmacokinetics beyond 6 hours. Furthermore a new slow-release misoprostol formulation was included in the study. METHODS: Pharmacokinetics of a novel slow-release (SR) oral misoprostol was compared during 12 h after administration to conventional misoprostol administered vaginally or sublingually. Thirty-three women requesting surgical abortion up to 12 weeks were randomly allocated to groups receiving a single dose of 400 microg conventional misoprostol administered vaginally or sublingually or 800 microg SR oral misoprostol. Blood samples were taken before (0 h) and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 h after misoprostol administration. Misoprostol acid (MPA) was determined in serum samples using liquid chromatography/tandem mass spectrometry. RESULTS: Three women did not complete the study. Serum concentrations reached their highest level following sublingual misoprostol (P<0.0001) and the time to peak concentration was shortest for this group (P=0.0094). The area under the curve (AUC) up to 12 h was greater following sublingual treatment than for the other alternatives (P<0.0001) and lowest for SR misoprostol. Cumulative serum levels of MPA did not increase beyond 6 h following sublingual and vaginal administration, while they continued to increase up to 12 h following SR misoprostol. CONCLUSIONS: The new SR form of misoprostol demonstrated lower peak levels and a lower AUC but longer lasting elevation in serum levels when compared to conventional misoprostol administered sublingually or vaginally. SR misoprostol may offer an alternative to repeated administration of conventional misoprostol.
RCT Entities:
BACKGROUND: It has been shown that the route of administration of misoprostol has a strong impact on the pharmacokinetic profile and result in different clinical efficacy. No study has so far evaluated the pharmacokinetics beyond 6 hours. Furthermore a new slow-release misoprostol formulation was included in the study. METHODS: Pharmacokinetics of a novel slow-release (SR) oral misoprostol was compared during 12 h after administration to conventional misoprostol administered vaginally or sublingually. Thirty-three women requesting surgical abortion up to 12 weeks were randomly allocated to groups receiving a single dose of 400 microg conventional misoprostol administered vaginally or sublingually or 800 microg SR oral misoprostol. Blood samples were taken before (0 h) and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 h after misoprostol administration. Misoprostol acid (MPA) was determined in serum samples using liquid chromatography/tandem mass spectrometry. RESULTS: Three women did not complete the study. Serum concentrations reached their highest level following sublingual misoprostol (P<0.0001) and the time to peak concentration was shortest for this group (P=0.0094). The area under the curve (AUC) up to 12 h was greater following sublingual treatment than for the other alternatives (P<0.0001) and lowest for SR misoprostol. Cumulative serum levels of MPA did not increase beyond 6 h following sublingual and vaginal administration, while they continued to increase up to 12 h following SR misoprostol. CONCLUSIONS: The new SR form of misoprostol demonstrated lower peak levels and a lower AUC but longer lasting elevation in serum levels when compared to conventional misoprostol administered sublingually or vaginally. SR misoprostol may offer an alternative to repeated administration of conventional misoprostol.
Authors: Yana Vorontsova; David M Haas; Kathleen Flannery; Andrea R Masters; Larissa L Silva; Rebecca C Pierson; Brittany Yeley; Graham Hogg; David Guise; Michael Heathman; Sara K Quinney Journal: Clin Transl Sci Date: 2022-06-12 Impact factor: 4.438