1991 Volume 6 Issue 6 Pages 919-932
The absorption, distribution, metabolism and excretion of NZ-105 were studied in male rats after a single (10mg/kg) administration of 14C-NZ-105.
1. Blood levels reached the maximum of 710.8ng eq./ml at 2hr after administration and decreased with half-life of 1.9hr until 11hr.
The absorption of radioactivity was significantly affected by the presence of food in the gastrointestinal tract.
2. The rates of radioactivity excretion in urine and feces within 120hr and bile within 24hr were 2.0, 93.8, and 60.2% of dose, respectively, demonstrating that the major route of excretion was biliary system.
3. The absorption ratio of radioactivity estimated from the sum of biliary and urinary excretions was calculated to be approximately 62%.
4. The radioactivity was high in the gastrointestinal tract and liver, followed by the adrenals. Radioactivity in each tissue was eliminated rapidly, and at 24hr was very low when compared with the maximum value.
5. The unchanged drug in the plasma accounted for 47.7% of total radioactivity at 2hr after administration, suggesting a lower first-pass effect in comparison with other dihydropyridine Ca channel blockers.
6. In plasma, major metabolites of NZ-105 were N-debenzylated compound (DBZ), N-dephenylated compound (DPH), oxidative deaminated compound (AL), AL-corresponding pyridine compound (ALP), unknown metabolite M-1 and M-25. They accounted for 2.5, 5.6, 3.5, 4.9, 3.8 and 14.4% of plasma total radioactivity, respectively, at 2hr after administration.
7. NZ-105 was metabolized by N-debenzylation, N-dephenylation, oxidative deamination, ester hydrolysis and oxidation of 1, 4-dihydropyridine ring to corresponding pyridine.
