Treprostinil

Molecular formula C23H34O5 Molecular weight 390.51 CAS Registry No 81846-19-7 

Sample preparation Extract 1 mL plasma with hexaneiethyl acetate 70 30. Evaporate the organic layer to dr3mess under a stream of nitrogen, reconstitute the residue with MeOH water 100 mM ammonium formaterformic acid 50 47.5 2.5 0.05, inject a 25 p.L aliquot. 

Mobile phase MeCN water 100 mM ammonium formateiformic acid 33.25 61.75 5 0.1 Flow rate 0.3 Injection volume 25 

Detector MS, PE Sciex API-Ill or API 365, ionspray, atmospheric pressure ionization, negative ionization 

Roscigno, R. DeUaMaestra, W. Hunt, T.L. Lai, A.A. Absolute bioavailability and pharmacokinetics of treprostinil sodium administered by acute subcutaneous infusion, 

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Treprostinil can be administered as supplied or diluted for IV infusion with sterile water for injection or 0.9% sodium chloride injection prior to administration. 

Hepatic function impairment In patients with mild or moderate hepatic insufficiency, decrease the initial dose of treprostinil to 0.625 ng/kg/min ideal body weight increase cautiously. Treprostinil has not been studied in patients with severe hepatic insufficiency. 

Subcutaneous infusion - Treprostinil is administered subcutaneously by continuous infusion, via a self-inserted subcutaneous catheter, using an infusion pump designed for subcutaneous drug delivery. 

For subcutaneous infusion, treprostinil is delivered without further dilution at a calculated subcutaneous infusion rate (mL/h) based on a patient s dose (ng/kg/min), weight (kg), and the vial strength (mg/mL) of treprostinil being used. The subcutaneous infusion rate is calculated using the following formula (conversion factor of 0.00006 = 60 min/h x 0.000001 mg/ng) ... 

Pharmacoiogy The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. 

Distribution - The volume of distribution of the drug in the central compartment is approximately 14 L per 70 kg ideal body weight. Treprostinil was 91% bound to human plasma protein. 

WefaboZ/sm- Treprostinil is substantially metabolized by the liver. Based on the results of in vitro human hepatic cytochrome P-450 studies, treprostinil... 

Excretion - The elimination of treprostinil is biphasic, with a terminal half-life of approximately 4 hours. Approximately 79% of an administered dose is excreted in the urine as unchanged drug (4%) and as the identified metabolites (64%). Approximately 13% of a dose is excreted in the feces. 

Treprostinil is contraindicated in patients with known hypersensitivity to the drug or to structurally related compounds. 

Route of administration Treprostinil is indicated for subcutaneous or IV use only. Renal/Hepatic function impairment Use caution in patients with hepatic or renal impairment. 

Lactation It is not known whether treprostinil is excreted in human milk or absorbed systemically after ingestion. 

Abrupt withdrawal or sudden large reductions in dosage of treprostinil may result in... 

Reduction in blood pressure caused by treprostinil may be exacerbated by drugs that by themselves alter blood pressure, such as diuretics, antihypertensive agents, or vasodilators. Because treprostinil inhibits platelet aggregation, there is also a potential for increased risk of bleeding, particularly among patients maintained on anticoagulants. 

Treprostinil Sodium (Remodulin) [Antihypertensive/ Vasodilator] Uses NYHA class II-IV pulm arterial HTN Action Vasodilation, inhibits pit aggregation Dose 0.625-1.25 ng/kg/min inj cont inf Caution [B, /-] Contra Component aUo-gy Disp Inj SE Additive effects w/ anticoagulants, antihypCTtensives inf site Rxns D (25%), N (22%), HA (27%) Interactions t Effects W/ antihypCTtensives t effects OF anticoagulants EMS t Effects of... 

The synthetic analogues of prostacyclin, be-raprost, treprostinil and iloprost, although also platelet aggregation inhibitors, are used to treat pulmonary arterial hypertension. 

Prostacyclin lowers peripheral, pulmonary, and coronary resistance. It has been used to treat both primary pulmonary hypertension and secondary pulmonary hypertension, which sometimes occurs after mitral valve surgery. A commercial preparation of prostacyclin (epoprostenol) is approved for treatment of primary pulmonary hypertension, in which it appears to improve symptoms and prolong survival. However, because of its extremely short plasma half-life, the drug must be administered as a continuous intravenous infusion through a central line. Several prostacyclin analogs with longer half-lives have been developed and treprostinil was recently approved for use in pulmonary hypertension (Horn, 2002). This drug is administered by continuous subcutaneous infusion. 

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