期刊
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
卷 128, 期 10, 页码 1459-1465出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/yakushi.128.1459
关键词
beraprost; cytochrome P450; drug-drug interaction; prostacyclin; chronic occlusive disease; primary pulmonary hypertension
Beraprost sodium (BPS), a chemically stable and orally active prostacyclin analogue used for the treatment of chronic occlusive disease and primary pulmonary hypertension, was investigated in terms of its drug-drug interaction mediated by cytochrome P450. In a metabolic enzyme characterization study using P450-expressing insect cell microsomes, beraprost (BP) was slightly metabolized in the presence of CYP2C8, but not metabolized by the other P450 isoforms (CYP1A1, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP4A11) at a concentration of 20 mu m. These results suggest that none of the P450 isoforms is a major metabolic enzyme of BP. In a P450 induction study using human hepatocytes, BP did not induce any P450 isoform (CYP1A2, CYP2C9, CYP2CI9, and CYP3A4) at concentrations of 1-100 mu m. Furthermore, in a P450 inhibition study using human liver microsomes, BP did not inhibit any P450 isoform (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2CI9, CYP2D6, and CYP3A4) at concentrations of 0.05-1 mu M. Therefore it is concluded that BP is not involved in drug-drug interaction mediated by P450 isoforms.
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