[Pharmacokinetics of verapamil and its N-dealkylated metabolites in patients with chronic ischemic heart disease undergoing long-term monotherapy].

Pharmacokinetics of verapamil (VP) and its main N-dealkylated metabolites (nor-VP, D-617 and D-620) was studied in 10 patients with chronic ischemic heart disease after administration of the first and last doses of the course of treatment (80-120 mg of VP 3-4 times per day for 4-7 months). The antipyrine test was used in 8 patients simultaneously with the study of pharmacokinetics of VP and its metabolites. At the end of the course a decrease of oral clearance of VP as compared with its beginning (from 3.02 to 1.57 l/min, p less than 0.01) and an increase of the drug half-life (from 6.48 to 9.49 hrs, p less than 0.01) were found. Half-lives of nor-VP and D-617 at the end of VP course (12.1 and 19.7 hrs, respectively) were also higher than at its beginning (8.7 and 14.2 hrs, respectively), half-life of D-620 underwent no significant changes (29.5 hrs at the beginning and 31.6 hrs at the end of VP course). At the end of VP course the patients exhibited a decrease of antipyrine clearance (to 28.7 versus 43.2 ml/min at the beginning of VP course, p less than 0.01) that indicates a reduced activity of oxidative microsomal enzymes of the liver due to long-term VP therapy. It is presumably one of the causes of decreased VP clearance at the course administration.