Prostaglandin prodrugs. 5.1 Prostaglandin E2 ethylene ketal.
In order to improve the chemical stability of prostaglanding E2 (2), prostaglanding E2 ethylene ketal (1) was prepred by direct ketalization of 2 with ethylene glycol in benzene. To establish a quantitative assessment of 1 as a chemically stable and orally active prodrug of 2, the hydrolysis of 1 to 2 and the subsequent dehydration of 2 to prostaglandin A2 (3) were followed at 25 degrees C and six pH's ranging from 2.0 to 6.5 by means of a high-pressure liquid chromatographic procedure. Kinetic results clearly indicate that 1 should be quantitively hydrolyzed back to the parent drug 2 dehydration of 2 to 3 are in the order of 1 h and 14 days, respectively. The preliminary data on the biological response after oral administration of 1 appeared to indicate the 1 is bioequivalent to 2.
D000080:Acetals / Q000138:chemical synthesis; D000818:Animals; D001682:Biological Availability; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005260:Female; D000882:Haplorhini; D006868:Hydrolysis; D007700:Kinetics; D008253:Macaca mulatta; D011247:Pregnancy; D011459:Prostaglandins E, Synthetic / Q000138:chemical synthesis* / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects
D000080:Acetals; D011459:Prostaglandins E, Synthetic