Predictive model of bosentan-induced liver toxicity in Japanese patients with pulmonary arterial hypertension.
Can J Physiol Pharmacol
; 98(9): 625-628, 2020 Sep.
Article
en En
| MEDLINE
| ID: mdl-32433892
ABSTRACT
Bosentan, an endothelin receptor antagonist, has been widely used as a first-line medication for the treatment of pulmonary arterial hypertension (PAH). It has been shown to improve symptoms of hypertension, exercise capacity, and hemodynamics and prolong time to clinical worsening. However, liver dysfunction is a major side effect of bosentan treatment that could hamper the optimal management of patients with PAH. Previously, we demonstrated, using drug metabolism enzymes and transporters analysis, that the carbohydrate sulfotransferase 3 (CHST3) and CHST13 alleles are significantly more frequent in patients with elevated aminotransferases during therapy with bosentan than they are in patients without liver toxicity. In addition, we constructed a pharmacogenomics model to predict bosentan-induced liver injury in patients with PAH using two single-nucleotide polymorphisms and two nongenetic factors. The purpose of the present study was to externally validate the predictive model of bosentan-induced liver toxicity in Japanese patients. We evaluated five cases of patients treated with bosentan, and one presented with liver dysfunction. We applied mutation alleles of CHST3 and CHST13, serum creatinine, and age to our model to predict liver dysfunction. The sensitivity and specificity were calculated as 100% and 50%, respectively. Considering that PAH is a rare disease, multicenter collaboration would be necessary to validate our model.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Modelos Estadísticos
/
Enfermedad Hepática Inducida por Sustancias y Drogas
/
Antagonistas de los Receptores de Endotelina
/
Bosentán
/
Hipertensión Arterial Pulmonar
Límite:
Adult
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Aged
/
Aged80
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Female
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Humans
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
Can J Physiol Pharmacol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón