Dược Động Học :
▧ Absorption :
Relatively rapid and complete after subcutaneous infusion, with an absolute bioavailability approximately 100%. In patients with mild (n=4) or moderate (n=5) hepatic insufficiency and portopulmonary hypertension following a subcutaneous dose of 10 ng per kg of body weight per min for 150 mins the AUC 0-∞ was increased 3-fold and 5-fold respectively.
▧ Volume of Distribution :
* 14 L/70 kg
▧ Protein binding :
Human plasma protein binding is approximately 91% in in vitro concentrations ranging from 330 to 10,000 µ/L.
▧ Metabolism :
Substantially metabolized by the liver, but the precise enzymes responsible are unknown. Five metabolites have been described (HU1 through HU5) however, the biological activity and metabolic fate of these are unknown. The chemical structure of HU1 is unknown. The metabolite HU5 is the glucuronide conjugate of treprostinil. The other metabolites are formed by oxidation of the 3-hydroxyoctyl side chain (HU2) and subsequent additional oxidation (HU3) or dehydration (HU4). Study results of in vitro human hepatic cytochrome P450 demonstrates that treprostinil does not inhibit CYP-1A2, 2C9, 2C19, 2D6, 2E1, or 3A. Whether treprostinil induces these enzymes has not been studied.
▧ Half Life :
Terminal elimination half-life is approximately 2 to 4 hours. Plasma half-life is 34 and 85 minutes for intravenous and subcutaneous infusion of the drug, respectively.