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Infect Dis Rep. 2015 Mar 16;7(1):5822. doi: 10.4081/idr.2015.5822. eCollection 2015 Feb 24.

Sildenafil and bosentan plasma concentrations in a human immunodeficiency virus- infected patient with pulmonary arterial hypertension treated with ritonavir-boosted protease inhibitor.

Author information

1
Second Infectious Diseases Unit, L. Spallanzani National Institute for Infectious Diseases , Rome.
2
Drug Abuse and Doping Unit, Department of Therapeutic Research and Medicines Evaluation, National Institute of Health , Rome.
3
Clinical Biochemistry and Pharmacology Laboratory, L. Spallanzani National Institute for Infectious Diseases , Rome.
4
III Cardiology Unit, S. Camillo-Forlanini Hospital , Rome, Italy.

Abstract

Sildenafil and bosentan are increasingly used for the treatment of pulmonary arterial hypertension (PAH) in HIV-infected patients. However, concerns exist about pharmacokinetic interactions among sildenafil, bosentan and antiretroviral drugs, including protease inhibitors (PI). We describe here the case of an HIV-infected patient with PAH, who was co-administered bosentan 125 mg twice daily and sildenafil 40 mg three times per day, together with a ritonavir-boosted PI-based antiretroviral therapy; plasma levels of bosentan, sildenafil, N-desmethylsildenafil, and PI were measured. The patient had a sildenafil Cthrough and Cmax of 276.94 ng/mL and 1733.19 ng/mL, respectively. The Cthrough and the Cmax of bosentan were 1546.53 ng/mL and 3365.99 ng/mL, respectively. The patient was able to tolerate as high sildenafil blood concentrations as 10 times those usually requested and did not report any significant adverse reaction to sildenafil during the follow-up period. Therapeutic drug monitoring should be considered during sildenafil therapy in patients concomitantly treated with ritonavir-boosted PI.

KEYWORDS:

bosentan; human immunodeficiency virus; protease inhibitors; pulmonary arterial hypertension; sildenafil

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