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...

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Bibliographic Details
Published inEuropean journal of drug metabolism and pharmacokinetics Vol. 16; no. 2; p. 75
Main Authors Caillé, G, Boucher, S, Spénard, J, Lakhani, Z, Russell, A, Thiffault, J, Grace, M G
Format Journal Article
LanguageEnglish
Published France 01.04.1991
Subjects
Aged
Biotransformation
Diltiazem - administration & dosage
Diltiazem - blood
Diltiazem - pharmacokinetics
Drug Administration Schedule
Female
Half-Life
Humans
Metabolic Clearance Rate
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Summary: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.
ISSN:0378-7966