Clin Pharmacol Ther. 2014 Jun;95(6):583-5. doi: 10.1038/clpt.2014.42.
CYP2C9, SLCO1B1, SLCO1B3, and ABCB11 polymorphisms in patients with bosentan-induced liver toxicity.Roustit M1, Fonrose X2, Montani D3, Girerd B3, Stanke-Labesque F4, Gonnet N5, Humbert M3, Cracowski JL1.
INSERM UMR 1042-HP2, Univ. Grenoble-Alpes, Grenoble, France
Clinical Pharmacology Unit, INSERM CIC1406, Grenoble University Hospital, Grenoble, France.
Laboratory of Pharmacology, Grenoble University Hospital, Grenoble, France.
Univ. Paris -Sud, AP-HP, Centre National de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie, Département Hospitalo Universitaire (DHU), Thorax Innovation (TORINO), Hôpital de Bicêtre, Le Kremlin Bicêtre, France
INSERM UMRS_999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
Clinical Pharmacology Unit, INSERM CIC1406, Grenoble University Hospital, Grenoble, France
Laboratory of Pharmacology, Grenoble University Hospital, Grenoble, France.
Clinical Pharmacology Unit, INSERM CIC1406, Grenoble University Hospital, Grenoble, France.
Abstract
Bosentan is an endothelin receptor antagonist used as a first-line treatment in pulmonary arterial hypertension (PAH). Its main adverse effect is a dose-dependent liver toxicity. CYP2C9*2 has recently been shown to be associated with hepatotoxicity in PAH patients. We conducted a nested case-control study to further explore the relationship between functional polymorphisms of gene products involved in bosentan pharmacokinetics (OATP1B1, OATP1B3, and CYP2C9) or hepatobiliary transporters affected by bosentan (ABCB11) and bosentan-induced liver toxicity.
Comment on Association of CYP2C9*2 with bosentan-induced liver injury. [Clin Pharmacol Ther. 2013]
PMID:24842639