Dose proportionality of treprostinil sodium administered by continuous subcutaneous and intravenous infusion.

This study assessed the relationship between dose and plasma concentration following administration of treprostinil sodium infusion therapy in pulmonary arterial hypertension patients. This was a multicenter, open-label, multiple-cohort, steady-state, pharmacokinetic study in subjects with pulmonary arterial hypertension receiving treprostinil by continuous intravenous or subcutaneous infusion at doses between 10 and 125 ng/kg/min. A blood sample was obtained from each patient at steady state and analyzed via a liquid chromatography/tandem mass spectrometry method.

The intramolecular asymmetric Pauson-Khand cyclization as a novel and general stereoselective route to benzindene prostacyclins: synthesis of UT-15 (treprostinil).

A general and novel solution to the synthesis of biologically important stable analogues of prostacyclin PGI(2), namely benzindene prostacyclins, has been achieved via the stereoselective intramolecular Pauson-Khand cyclization (PKC). This work illustrates for the first time the synthetic utility and reliability of the asymmetric PKC route for synthesis and subsequent manufacture of a complex drug substance on a multikilogram scale. The synthetic route surmounts issues of individual step stereoselectivity and scalability.