Diltiazem pharmacokinetics in elderly volunteers after single and multiple doses.
In young healthy volunteers diltiazem does not have linear kinetics between single and multiple doses. Elimination half-life increases and gives AUC's and Cmax higher than those predicted from single dose data. Kinetics of diltiazem were assessed in 16 healthy elderly after a single 60 mg dose and in 24 healthy elderly after 60 mg every 8 h for 7 days. Thirteen participants completed both studies. Elimination half-life, AUC0-24, AUC0-infinity, and Cmax were (mean +/- SE) 7.4 (1.2) h, 349 (34) ng/ml.h, 392 (44) ng/ml.h, and 43 (5) ng/ml respectively after a single dose. After multiple doses elimination half-life, AUC0-48, AUC0-infinity, Cmax and Cmin were respectively 5.7 (0.3) h, 974 (107) ng/ml.h, 1022 (108) ng/ml.h, 102 (7) ng/ml and 43 (5) ng/ml. Exploratory statistics on the 13 volunteers common to both studies showed that the ratio of AUC desacetyl-diltiazem (DAD)/AUC diltiazem rose between single and multiple doses while elimination half-life of both diltiazem and N-desmethyl-diltiazem (MA), tmax, and AUC MA/AUC diltiazem were not affected. The conclusion of this study is that elimination half-life of diltiazem does not increase in elderly between single and multiple doses, possibly due to an increased biotransformation into DAD.
Department of Pharmacology, Université de Montréal, Canada.
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G
Caillé
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Boucher
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Spénard
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Lakhani
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Russell
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Thiffault
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MG
Grace
D000368:Aged; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004110:Diltiazem / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male
C037769:deacetyldiltiazem; D004110:Diltiazem; C052825:N-monodemethyldiltiazem