gemeprost

Absorption

Systemic absorption of gemeprost is limited with about 12-28% of administered dose of gemeprost reaching the systemic circulation . Following vaginal administration, peak plasma concentration is reached after 2-3 hours .

Toxicity

Serious or life-threatening adverse effects include coronary spasms with subsequent myocardial infarctions and uterine rupture following prolonged uterine hypertonia or abnormal uterine pain. More common adverse effects are nausea, vomiting, loose stools, diarrhea, lower abdominal or back pain, headache, mild pyrexia and flushing. Less common side effects include hypotension, chest pain palpitations, tachycardia, muscle weakness, dyspnea, chills and headache. Oral LD50 is 300 mg/kg in mouse, 980 mg/kg in rat and 3200 mg/kg in rabbit .

Description

Gemeprost, a metabolically stabilized analog of PGE1, has been demonstrated to reliably induce termination of early pregnancy when administered as a vaginal suppository. Its effect is presumably due to both uterine contraction and rapid decline of steroid hormone levels. Minimal side effects have been reported.

Originator

Ono (Japan)

The Uses of gemeprost

Gemeprost is an analogue of Prostaglandin (P838600). Gemeprosts, similarly to Nitric Oxide donors, induce uterine cervical dilation and are used before surgical termination of pregnancy.

The Uses of gemeprost

Prostaglandin.

Background

Gemeprost is a prostaglandin E1 (PGE1) analog and antiprogestogen used for preoperative dilation of the cervix before surgical abortion. It is available as vaginal suppositories and also used in combination with the antiprogestin and mifepristone for termination of 1st- and 2nd-trimester pregnancy . It is not FDA-approved but available in Japan marketed as Preglandin.

Indications

Indicated for the softening and dilatation of the cervix uteri prior to transcervical, intrauterine operative procedures in the first trimester of pregnancy or facilitating therapeutic termination of pregnancy in patients in the second trimester of gestation.

Definition

ChEBI: Gemeprost is an aliphatic alcohol.

Manufacturing Process

Synthesis of 9-oxo-1α,15α-bis-(2-tetrahydropyranyloxy)-16,16-dimethylprosta-trans-2, trans-13-dienoic acid: 4 g of ethyl 9α-hydroxy-11α15α-bis-(2- tetrahydropyranyloxy)-16,16-dimethyl-prosta-trans-2,trans-13-dienoate were dissolved in 130 ml of a mixture of ethanol-water (3:1), mixed with 3.9 g of potassium hydroxide and stirred at 25°C for 2 hours. The reaction mixture was acidified with aqueous solution of oxalic acid to pH 5, and diluted with 100 ml of water, extracted with ethyl acetate. The extracts were washed with water, dried over sodium sulfate and concentrated under reduced pressure to obtain 3.88 g of 9α-hydroxy-11α,15α-bis-(2-tetrahydropyranyloxy)-16,16- dimethyl-prosta-trans-2,trans-13dienoic acid.
The obtained compound 2.46 g were dissolved in 72 ml of diethyl ether and stirred at 3°C. To which a solution of manganese sulfate (15 g), 3.1 g of chromium trioxide, 72 ml of water and 3.5 ml of sulfuric acid was added. After stirring for 3.5 hours at 3°C, extracted with diethyl ether. The organic layer was washed with water, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using ethyl acetate-benzene (1:1) as eluent to give 2.35 g of the title compound.
Synthesis of 16,16-dimethyl-trans-δ2-PGE1: 2.35 g of the bistetrahydropyranyl ether were dissolved in 6 ml of tetrahydrofuran and 60 ml of 65%-acetic acid aqueous solution and the solution stirred at 60°C to 70°C for 20 minutes. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using ethyl acetate-cyclohexane (2:3) as eluent to yield 270 mg of the title compound.

brand name

CERVAGEM

Therapeutic Function

Prostaglandin, Cervical softener

Pharmacokinetics

Gemeprost softens and dilates of the cervix prior to transcervical intrauterine operative procedures. It is a prostaglandin E1 analog that potently stimulates uterine contractions and causes cervical ripening and relaxation .

Metabolism

After intravenous administration, gemeprost is rapidly metabolized via hydrolysis to the free acid with half life of 10-15 minutes. The free acid is then inactivated by β- and ω-oxidation .