[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.
Rumiantsev
D O
DO
Piotrovskiĭ
V K
VK
Metelitsa
V I
VI
Riabokon'
O S
OS
Kokurina
E V
EV
D000328:Adult; D000983:Antipyrine / Q000493:pharmacokinetics; D002908:Chronic Disease; D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D008875:Middle Aged; D009570:Nitriles; D013997:Time Factors; D014700:Verapamil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use
D009570:Nitriles; C016906:alpha-(3-aminopropyl)-3,4-dimethoxy-alpha-(1-methylethyl)benzeneacetonitrile; C482241:2-(3,4-dimethoxyphenyl)-5-amino-2-isopropylvaleronitrile; C016904:norverapamil; D014700:Verapamil; D000983:Antipyrine
Farmakokinetika verapamila i ego N-dealkilirovannykh metabolitov u bol'nykh khronicheskoĭ ishemicheskoĭ bolezn'iu serdtsa v usloviiakh dlitel'noĭ monoterapii.