Dinoprostone (PGE2) is a naturally-occurring biomolecule. It is found in low concentrations in most tissues of the body and functions as a local hormone (1-3). As with any local hormone, it is very rapidly metabolized in the tissues of synthesis (the half-life estimated to be 2.5-5 minutes). The rate limiting step for inactivation is regulated by the enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) (1,4). Any PGE2 that escapes local inactivation is rapidly cleared to the extent of 95% on the first pass through the pulmonary circulation (1,2).
In pregnancy, PGE2 is secreted continuously by the fetal membranes and placenta and plays an important role in the final events leading to the initiation of labor (1,2). It is known that PGE2 stimulates the production of PGF2α which in turn sensitizes the myometrium to endogenous or exogenously administered oxytocin. Although PGE2 is capable of initiating uterine contractions and may interact with oxytocin to increase uterine contractility, the available evidence indicates that, in the concentrations found during the early part of labor, PGE2 plays an important role in cervical ripening without affecting uterine contractions (5-7). This distinction serves as the basis for considering cervical ripening and induction of labor, usually by the use of oxytocin (8-10), as two separate processes.
PGE2 plays an important role in the complex set of biochemical and structural alterations involved in cervical ripening. Cervical ripening involves a marked relaxation of the cervical smooth muscle fibers of the uterine cervix which must be transformed from a rigid structure to a softened, yielding and dilated configuration to allow passage of the fetus through the birth canal (11-13). This process involves activation of the enzyme collagenase, which is responsible for digestion of some of the structural collagen network of the cervix (1, 14). This is associated with a concomitant increase in the amount of hydrophilic glycosaminoglycan, hyaluronic acid and a decrease in dermatan sulfate (1). Failure of the cervix to undergo these natural physiologic changes, usually assessed by the method described by Bishop (15, 16), prior to the onset of effective uterine contractions, results in an unfavorable outcome for successful vaginal delivery and may result in fetal compromise. It is estimated that in approximately 5% of pregnancies the cervix does not ripen normally (17). In an additional 10-11% of pregnancies, labor must be induced for medical or obstetric reasons prior to the time of cervical ripening (17).
The delivery rate of PGE2 in vivo is about 0.3 mg/hour over a period of 12 hours. The controlled release of PGE2 from the hydrogel insert is an attempt to provide sufficient quantities of PGE2 to the local receptors to satisfy hormonal requirements. In the majority of patients, these local effects are manifested by changes in the consistency, dilatation and effacement of the cervix as measured by the Bishop score. Although some patients experience uterine hyperstimulation as a result of direct PGE2- or PGF2α-mediated sensitization of the myometrium to oxytocin, systemic effects of PGE2 are rarely encountered. The insert is fitted with a biocompatible retrieval system which facilitates removal at the conclusion of therapy or in the event of an adverse reaction.
No correlation could be established between PGE2 release and plasma concentrations of PGEm. The relative contributions of endogenously and exogenously released PGE2 to the plasma levels of the metabolite PGEm could not be determined. Moreover, it is uncertain as to whether the measured concentrations of PGEm reflect the natural progression of PGEm concentrations in blood as birth approaches or to what extent the measured concentrations following PGE2 administration represent an increase over basal levels that might be measured in control patients.
Table 2 : Efficacy of Cervidil (dinoprostone) in Double Blind Studies
|Time to Delivery (hours)|
|Time to Onset of Labor (hrs)|
|*Treatment success was defined as Bishop score increase at 12 hours of > 3, vaginal delivery within 12 hours or Bishop score at 12 hours > 6. These studies were not designed with the power to show differences in cesarean section rates between Cervidil and placebo groups and none were noted.|
1. Physiology of Labor In: Williams Obstetrics. Eds. Pritchard, J. A., MacDonald, P. C., and Gant, N.F. Appleton-Century-Crofts, Conn, Pp 295-321, (1985).
2. Rall, T. W. and Schliefer, L. S. Oxytocin, prostaglandin, ergot alkaloids, and other drugs; tocolytics agents, In: The Pharmacological Basis of Therapeutics. Eds. Gilman, A.G., Goodman, L.S., Rall, T.W., and Murad, F. MacMillan, Publ. Co., New York, Pp. 926-945, (1985).
3. Casey, M.L. and MacDonald, P.C. The initiation of labor in women: Regulation of phospholipid and arachidonic acid metabolism and of prostaglandin production. Semin. Perinat. 10:270-275, (1986).
4. Casey, M.L., MacDonald, P.C. and Mitchell, M.D. Stimulation of prostaglandin E2 production in amnion cells in culture by a substance(s) in human fetal urine. Biochem. Biophys. Res. Comm. 114:1056, (1983).
5. Olson, D.M., Lye, S.J., Skinner, K. and Challis, J.R.G. Prostanoid concentrations in maternal/fetal plasma and amniotic fluid and intrauterine tissue prostanoid output in relation to myometrial contractility during the onset of adrenocorticotropin-induced preterm labor in sheep, 116: 389-397, (1985).
6. Ledger, W.L., Ellwood, D.A., and Taylor, M.J. Cervical softening in late pregnant sheep by infusion of prostaglandin E-2 into cervical artery. J. Reprod. Fert. 69, 511-515, (1983).
7. Olson, D.M., Lye, S.J., Skinner, K. and Challis, J.R.G. Early changes in prostaglandin concentrations in ovine maternal and fetal plasma, amniotic fluid and from dispersed cells of intrauterine tissues before the onset of ACTH-induced pre-term labor. J. Reprod. Fert., 71: 45-55, (1984).
8. Caldeyro-Barcia, R. and Posiero, J. Oxytocin and the contractility of the human uterus, Ann, N. Y. Acad. Sci. 75:813, (1959).
9. Posiero, J. and Noriega-Guerra, L. Dose-response relationships in uterine effects of oxytocin infusion. Oxytocin. Eds., Caldeyro-Barcia, R. and Heller, J. Pergamon Press, New York, (1961).
10. Cibils, L. Enhancement of induction of labor. In: Risks in the Practice of Modern Obstetrics. Aldjem, S. Ed. Mosby Publishing, St. Louis, (1972).
11. Bryman, I., Lindblom, B., and Norstrom, A. Extreme sensitivity of cervical musculature to prostaglandin E2 in early pregnancy. Lancet, 2:1471, (1982).
12. Thiery, M. Induction of labor with prostaglandins. In: Human Parturition. Eds. Keirse, M.J.N.C., Anderson, A.B.M., and Gravenhorst, J.B. Martinus Nijhoff Publ., Boston, 155-164, (1979).
13. Thiery, M. and Amy, J.J. Induction of labor with prostaglandins. In:Advances in Prostaglandin Research. Prostaglandin and Reproduction, Karim, S.M.M., Ed., MTP, Lancaster, Pp. 149-228, (1975).
14. MacLennan, A.H., Katz, M., and Creasey, R. The morphologic characteristics of cervical ripening induced by the hormones relaxin and prostaglandin F2 in a rabbit model. Am. J. Obstet. Gynecol, 152:910696, (1985).
15. Bishop, E. Elective induction of labor. Obstet & Gynecol, 5: 519-527, (1955).
16. Bishop, E. Pelvic scoring for elective induction. Obstet & Gynecol. 24: 266-268, (1969).
17. Thiery, M. Preinduction cervical ripening. In: Obstetrics and Gynecology Annual, Vol. 12, Ed. Wynn, R. M. Appleton-Century-Crofts, New York, Pp. 103-146, (1983).
19. De Abajo FJ et al. Labor induction with dinoprostone or oxytocin and postpartum disseminated intravascular coagulation: a hospital-based case-control study. Am J Obs Gynecol, 2004, 191: 1637-1643.
Last reviewed on RxList: 6/17/2010
This monograph has been modified to include the generic and brand name in many instances.
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