Metabolism of nipradilol by liver homogenates from different species. I. Comparative studies on the denitration of nipradilol and other organic nitrates

Abstract

1. Nipradilol (NP) was metabolized mainly in liver and denitrated and/or hydroxylated metabolites were formed. NP was not metabolized in heart or lung, and was stable in blood.

2. Denitration of NP was catalysed mainly by glutathione-dependent organic nitrate reductase in liver cytosol, and the hydroxylation was catalysed by liver-microsomal enzymes.

3. Denitration activity for NP was far lower than that for nitroglycerol and isosorbide dinitrate with liver homogenates of several animal species.

4. A marked species difference was found in the denitration activity for NP; dog liver was especially low compared with rabbit, rat and mouse liver.

Key Words:

• anti-hypertensive
• anti-anginal agent
• denitration
• isosorbide dinitrate
• metabolism in vitro
• nipradilol
• nitroglyerol
• species difference