イロプロスト

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Cardiovascular Agents; Prostaglandins, Synthetic; Vasodilator Agents

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Pharmaceuticals

Danger

H301 (98.5%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P261, P262, P264, P270, P271, P280, P301+P316, P302+P352, P304+P340, P316, P318, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 66 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

Iloprost

DILI Positive

DOI:10.1016/j.drudis.2019.09.022

B01AC11

B - Blood and blood forming organs

QB - Blood and blood forming organs

Iloprost is a synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. There are two diastereoisomers of iloprost and the 4S isomer is reported to exhibit a higher potency in dilating blood vessels compared to the 4R isomer. In patients with primary pulmonary hypertension, iloprost decreased pulmonary vascular resistance and pulmonary artery pressure. Iloprost was shown to inhibit platelet aggregation, but whether this effect contributes to its vasodilatory action has not been elucidated. Iloprost is reported to attenuate ischemia-induced tissue injury. When administered intravenously in patients with peripheral vascular conditions such as critical leg ischemia and delayed amputation, iloprost was shown to promote cytoprotection. In isolated animal heart preparations and in intact animals with ischemia-reperfusion injury, preserved myocardial function was observed following iloprost administraion.

In pulmonary arterial hypertension, endothelial vasoactive mediators such as nitric oxide and prostacyclin are released to induce vasoconstriction. Iloprost mimics the biological actions of prostacyclin, a short-lived prostanoid and potent vasodilator mainly produced in the vascular endothelium. The exact mechanism of iloprost in cytoprotection has not been fully elucidated; however, it is proposed that iloprost decreases catecholamine outflow from sympathetic nerve terminals, preserves mitochondrial function, and reduces oxidative stress. Decreased neutrophil accumulation and membrane stabilization have also been suggested.

In vitro studies reveal that cytochrome P450-dependent metabolism plays only a minor role in the biotransformation of iloprost. Iloprost is metabolized principally via β-oxidation of the carboxyl side chain. The main metabolite is tetranor-iloprost, which was shown to be pharmacologically inactive in animal experiments. In rabbits, dinor-iloprost has also been identified as a drug metabolite.

JED5K35YGL

ILOPROST

Established Pharmacologic Class [EPC] - Prostacycline

Chemical Structure [CS] - Prostaglandins I

Iloprost is a Prostacycline.

ILOPROST

Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.

Drugs used to cause dilation of the blood vessels.

Following inhalation of iloprost (5 mcg) patients with pulmonary hypertension have iloprost peak plasma levels of approximately 150 pg/mL. Iloprost was generally not detectable in plasma 30 minutes to one hour after inhalation. The absolute bioavailability of inhaled iloprost has not been determined. When iloprost was administered via intravenous infusion at a rate of 2 ng/kg/min, steady-state plasma concentrations were 85 ng/L.

Unchanged iloprost and its metabolites are mainly excreted in urine. About 70% of the drug and metabolites undergo renal excretion. Following the administration of intravenous infusion at the rate of 2 ng/kg/min and oral dose at 0.1 ug/kg, fecal excretion was 12% and 17%, respectively.

Following intravenous infusion, the apparent steady-state volume of distribution was 0.7 to 0.8 L/kg in healthy subjects.

Clearance in normal subjects was approximately 20 mL/min/kg.