Evaluation of drug-drug interaction potential of beraprost sodium mediated by P450 in vitro

Yakugaku Zasshi. 2008 Oct;128(10):1459-65. doi: 10.1248/yakushi.128.1459.


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 (CYP1A2, [corrected] CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP4A11) at a concentration of 20 microM. 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, CYP2C19, and CYP3A4) at concentrations of 1-100 microM. Furthermore, in a P450 inhibition study using human liver microsomes, BP did not inhibit any P450 isoform (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) at concentrations of 0.05-1 microM. Therefore it is concluded that BP is not involved in drug-drug interaction mediated by P450 isoforms.

MeSH terms

  • Antihypertensive Agents / pharmacology
  • Arterial Occlusive Diseases
  • Chronic Disease
  • Cytochrome P-450 Enzyme System* / metabolism
  • Drug Interactions
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / pharmacology
  • Humans
  • Hypertension, Pulmonary
  • In Vitro Techniques
  • Isoenzymes
  • Microsomes, Liver / enzymology
  • Platelet Aggregation Inhibitors / pharmacology


  • Antihypertensive Agents
  • Isoenzymes
  • Platelet Aggregation Inhibitors
  • beraprost
  • Cytochrome P-450 Enzyme System
  • Epoprostenol