Pharmacokinetics and metabolism of ryodipine in rats

2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1, 4-dihydropyridine (ryodipine, PP-1466) at oral administration in the form of a suspension with Tween (polysorbate) 80 addition is comparatively rapidly absorbed in the gastro-intestinal tract and circulates in blood for a long period of time. PP-1466 practically does not bind to plasma proteins. The drug is mainly excreted via the kidneys and with faeces by 49 and 46% of the dose administered after 96 h, respectively. PP-1466 metabolites are present in rat urine-2,6-dimethyl-4-arylpyridine-3,5-dicarbonic acid derivatives: oxidation product of PP-1466 dihydropyridine cycle into pyridine one, products of partial or complete hydrolysis of ester groups of PP-1466 oxidized form, lactones. There have been performed the synthesis of labelled 14C-PP-1466 as well as counter-synthesis of PP-1466 metabolites. Unchanged PP-1466 is not detected in urine.