Serum profile of isosorbide mononitrate after vaginal administration in the third trimester

Abstract

Vaginally administered nitric oxide donors such as isosorbide mononitrate have been used to ripen the uterine cervix in pregnancy. The pharmacokinetics of isosorbide mononitrate following vaginal administration are unknown. Serum levels of isosorbide mononitrate were determined at baseline and 60, 180 and 360 minutes after vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women scheduled for induction of labour at term. Serum levels of isosorbide mononitrate continued to rise up to 360 minutes after isosorbide mononitrate insertion, with mean (SD) final levels of 337 (94) Ag/L following isosorbide mononitrate 40 mg and 144 (47) Ag/L following isosorbide mononitrate 20 mg, P < 0.01.

Nitric oxide donor isosorbide mononitrate for pre‐induction cervical ripening at 41 weeks' gestation: A randomized controlled trial

“…Although significant tachycardia and hypotension have also been noted with vaginal ISMN therapy, they have been found to be of no clinical significance. [17][18][19] Prenatal assessment of the fetus, as well as assessment of the new born have not shown any adverse effects of vaginal ISMN treatment. 16,18,20 There were no differences in the CS rates either at 48 h or at 72 h after the intervention between the ISMN-SR and the control groups.…”

“…No clinically significant hemodynamic changes were detected in the current study. Although significant tachycardia and hypotension have also been noted with vaginal ISMN therapy, they have been found to be of no clinical significance 17–19 . Prenatal assessment of the fetus, as well as assessment of the new born have not shown any adverse effects of vaginal ISMN treatment 16,18,20 …”

“…Therefore, all the subjects were monitored for 10 h but no clinically significant adverse effects were noted. It has been shown that although oral administration of ISMN results in peak serum levels occurring within 2 hours, vaginal ISMN results in peak serum levels being achieved much later; 6 hours or more after administration 19 . This could be due to the drug being first transmitted to the cervix and body of the uterus; the first uterine pass mechanism 25 …”

“…Therefore the role of NO donors as preinduction cervical ripening agents in pregnancies at term is being studied 15–18 . The maternal and fetal hemodynamic changes that occur after vaginal administration of ISMN for preinduction cervical ripening at term have not been found to be clinically significant 18–20 …”

“…[15][16][17][18] The maternal and fetal hemodynamic changes that occur after vaginal administration of ISMN for preinduction cervical ripening at term have not been found to be clinically significant. [18][19][20] ISMN is normally used in a dose ranging from 20 to 120 mg daily in divided doses or 60-120 mg once daily in a sustained release form (ISMN-SR) in the prophylactic management of angina pectoris. 21 When given orally, ISMN achieves peak levels in serum in 30 min and has a half life of approx.…”