Lack of a pharmacokinetic interaction between oral treprostinil and bosentan in healthy adult volunteers.

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Gotzkowsky SK, Dingemanse J, Lai A, Mottola D, Laliberte K

Lack of a pharmacokinetic interaction between oral treprostinil and bosentan in healthy adult volunteers.

J Clin Pharmacol. 2010 Jul;50(7):829-34. doi: 10.1177/0091270009351173. Epub 2010 Feb 4.

PubMed ID

20133511 [ View in PubMed

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Abstract

Treprostinil diethanolamine is an oral prostacyclin analog currently being evaluated for the treatment of pulmonary arterial hypertension (PAH). Treprostinil is metabolized primarily by cytochrome P450 (CYP) 2C8 with minor contribution from CYP2C9. It is expected that oral treprostinil will be administered with bosentan, approved for the treatment of PAH and known to induce CYP2C9 and 3A4. This study evaluated whether a drug interaction exists between oral treprostinil, bosentan, and its active metabolite Ro 48-5033 during co-administration. Twenty-four participants were randomized in a 3-way crossover study to oral treprostinil 1 mg twice daily, bosentan 125 mg twice daily, and oral treprostinil 1 mg twice daily and bosentan 125 mg twice daily. Treprostinil geometric mean ratios (GMRs) (90% confidence interval [CIs]) for steady-state AUC(0-12) and C(max) (combination/treprostinil) were 0.92 (0.83, 1.03) and 0.96 (0.83, 1.11), respectively, whereas bosentan GMRs (combination/bosentan) were 1.02 (0.95, 1.10) and 1.04 (0.94, 1.15), respectively, and Ro 48-5033 GMRs were 0.99 (0.93, 1.06) and 1.03 (0.94, 1.13). In conclusion, because the GMR and 90% CI are within the equivalence interval of 0.8 to 1.25, co-administration of oral treprostinil and bosentan did not result in a pharmacokinetic interaction for either agent.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Treprostinil	Cytochrome P450 2C9	Protein	Humans	Unknown	Substrate	Details