THE USE OF PROSTAGLANDIN ANALOGUES FOR PREGNANCY TERMINATION

Abstract

Prostaglandins, which are naturally occurring fatty acids, have revolutionised the treatment of termination of pregnancy; induced abortion has become safer nowadays. The clinical use of prostaglandins in patients developed rather more rapidly than it would have been possible for any other new chemical product. Following biosynthesis in 1965, it was used in women in 1968. Its rapid clinical application in pharmaco1ogical doses was probably helped by the fact that prostaglandins are naturally occurring compounds in the human body. The University Department of Obstetrics and Gynaecology was fortunate to have Research Professor S M M Karim join its ranks in 1973. He brought with him his immense expertise in prostaglandin research. At about that time too abortion laws were liberalized in Singapore and there was an increased demanded for abortion services. There was therefore clinical material in abundance for the investigation of synthetic analogues of prostaglandins for pregnancy termination. Since in those early years there was no local ethical committee to review such research, the responsibility of ensuring ethical application of these new analogues fell squarely on those involved in this work. The synthetic analogues were obtained mainly from Schering, Upjohn and ONO Pharmaceutical firms where the basic animal toxicology on their respective compounds had been completed. The compounds were then tested in the Research laboratories of the University Unit for in vitro activity on guinea pig ileum, bronchial muscle and animal and human uterine myometrial strips and then given in vivo to baboons which were carefully monitored for adverse effects. If the drug successfully passed these stages and was found to be promising, it was taken by a member of our research team. When its safety was confirmed it was applied to a limited number of patients seeking abortion after obtaining informed consent. If this Phase I study showed promise and there were no major side effects, the analogue was tested in larger numbers of women. Very often a large number of analogues had to be tested before one or two could be found with clinical application. Even after an analogue showed promise in early clinical application, the optimum dose, route of administration and formulation would have to be determined to obtain maximal efficacy with minimum side effects. The present study concentrates on these dose-ranging and efficacy studies which have been done with some prostaglandin analogues for procuring pregnancy termination. Nalador (sulprostone) and Cervagem (gemeprost) are two compounds which are now commercially available which have been taken through clinical trial and development by the prostaglandin research team of the University Department of Obstetrics and Gynaecology.