Cervidil - Pharmaceutical Information, Clinical Trials, Detailed Pharmacology, Toxicology
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Cervidil - Scientific Information

Manufacture: Ferring Pharmaceuticals
Country: Canada
Condition: Labor Induction
Class: Uterotonic agents
Form: Vaginal (e.g., douche, pessary, etc.)
Ingredients: dinoprostone, hydrogel polymer, macrogol 8000, dicyclohexylmethane-4,4’diisocyanate, 1,2,6-hexanetriol, polyester retrieval system

Pharmaceutical Information

Drug Substance

Proper Name: Ditdoprostone
Chemical Names: (1)Prosta-5,13-dien-1-oic acid, 11,15-dihydroxy-9-oxo-,(5Z,11α,13E,-15S)-

(2)(E,Z)-(1R,2R,3R)-7-[3-Hydroxy-2-[(3S)-(3-hydroxy-1-octenyl)]-5-oxocyclopentyl]-5-heptenoic acid

(3)Prostaglandin E2

Structural Formula:
Molecular Formula: C20H32O5
Molecular Weight: 352.47

Description

Dinoprostone occurs as a white to off-white crystalline powder. It has a melting point within the range of 65o to 68oC. Dinoprostone is freely soluble in ethanol, methylene chloride, ethyl acetate and chloroform, and very slightly soluble in n-hexane. Aqueous solubility is 1.05 mg/mL at 25oC.

Composition

Each insert contains 10 mg of dinoprostone in 236 mg of a cross-linked polyethylene oxide/urethane polymer which is a semi-transparent, beige coloured, flat, 0.8 mm thick rectangular slab measuring 29 mm by 9.5 mm. The insert and its retrieval system, made of polyester yarn, are non-toxic and when placed in a moist environment, absorb water, swell, and release dinoprostone.

Toxicology

Toxicology studies have been conducted on PGE2, on the hydrogel polymer and on the insert retrieval system.

There is little information specifically related to PGE2 toxicity because of its rapid inactivation in the body. A study in chicken embryos and newly hatched chicks showed that there was no discernable PGE2-related lethality following administration of doses between 10-5 and 10 -8M to embryos and proportionally larger doses to chicks.

The hydrogel polymer showed no evidence of toxicity in a cytotoxicity study in mouse fibroblast cultures or in an intramuscular implantation test in rabbits. Dietary and oral toxicity studies of the hydrogel polymer in rats and dogs were conducted for periods between 10 and 36 days and showed no evidence of toxicity.

In vitro unscheduled DNA synthesis assays on primary rat hepatocytes showed no evidence of mutagenicity for PGE2 at doses up to 5000 Fg/mL.

PGE2 administered subcutaneously to female mice at doses up to 50 Fg/kg/day during days 11 to 17 of pregnancy had a masculinizing effect on the genital tract of female fetuses. The results of this study and a related in vitro study using female genital duct cultures suggest that PGE2 plays a role in androgen-dependent masculine differentiation.

The insert retrieval system which is composed of the polyester material Dacron T56 and the material itself were evaluated in in vitro cytotoxicity tests, systemic toxicity tests in mice, intramuscular implantation tests in rabbits, hemolysis tests, pyrogenicity tests, intracutaneous reactivity tests in rabbits, skin irritation tests in guinea pigs and vaginal irritation tests in rabbits. There was no evidence of toxicity in any of the studies.

The results of an in vitro test using Staphylococcus aureus predict no association between the use of the hydrogel insert and toxic shock syndrome.