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Diltiazem pharmacokinetics in elderly volunteers after single and multiple doses

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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 60mg 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−∞, 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−∞, Cmax and Cmin in 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), W*, 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.

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Authors and Affiliations

  1. Department of Pharmacology, Université de Montréal, Montréal, Canada

    G. Caillé & S. Boucher

  2. Department of Medicine, University of Alberta, Edmonton, Canada

    Z. Lakhani, A. Russell, J. Thiffault & M. G. Grace

  3. Nordic Laboratories, St Martin Branch, PO Box 403, H7S 2A4, Laval, Quebec, Canada

    J. Spénard

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  1. G. Caillé
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Caillé, G., Boucher, S., Spénard, J. et al. Diltiazem pharmacokinetics in elderly volunteers after single and multiple doses. European Journal of Drug Metabolism and Pharmacokinetics 16, 75–80 (1991). https://doi.org/10.1007/BF03189878

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  • DOI: https://doi.org/10.1007/BF03189878

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