Altered diltiazem metabolism in the neonatal rabbit following intra-uterine chronic exposure to diltiazem

1. Diltiazem undergoes extensive metabolism in hepatic and extra hepatic ti ssues. Deacetyldiltiazem (M1) and N-demethyldiltiazem (MA) are tow of the m ain basic metabolites of diltiazem that retain harmacological activity. Thi s drug impairs its own metabolism after chronic administration in the adult patient. The study examines the possiblity that intra-uterine exposure fol lowing chronic maternal therapy with DTZ from mid-gestation to term also im pairs DTZ metabolism of its offspring. 2. DTZ was incubate in homogenates from liver, lung, brain and gut in the w ho blood of animals whose mothers were exposed to chronic treatment with di ltiazem or unexposed (placebo), DTZ and its metabolites were assayed by HPL C. 3. DTZ deacetylase activity observed in liver, lung and brain homogenates f rom 1-, 9- and 16-day-old rabbits was significant lower in exposed animals. In gut homogenates, this age-dependent effect was not so clear. This inhib ition could not be detected in any organ of 30-day-old rabbits. On the othe r hand, the activity observed in whole blood was not altered in intra-uteri ne chronic exposure to DTZ. 4. DTZ demethylase activity showed no differences in tissue homogenates and in whole blood from exposed compared with the unexposed rabbit. 5. In conclusion, the findings suggest that intra-uterine chronic exposure to DTZ has a large and prolonged effect on newborn metabolism deacetylase a ctivity compared with the unexposed rabbit.