Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose

P. K.F. Yeung, C. Prescott, C. Haddad, T. J. Montague, C. McGregor, M. A. Quilliam, M. Xei, R. Li, P. Farmer, G. A. Klassen

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36 Scopus citations

Abstract

Plasma concentrations and urinary excretion of DTZ and its metabolites were determined in 20 healthy volunteers (10 males and 10 females) after they had each been given a single oral 90 mg dose of DTZ. DTZ and six of its metabolites which included N-monodesmethyl DTZ (M A), deacetyl DTZ (M 1), deacetyl N-monodesmethyl DTZ (M 2), deacetyl O-desmethyl DTZ (M 4) and deacetyl DTZ N-oxide (M 1NO) and deacetyl N,O-didesmethyl DTZ (M 6), were determined by a sensitive and specific HPLC assay. The major metabolites measurable in the plasma of all the volunteers were M A, M 1, and M 2. The terminal half-lives (t 1/2) of M 1 and M 2 were considerably longer than those of DTZ and M A. Less than 5% of the dose was excreted as unchanged DTZ in the urine over the 24 h period. The major urinary metabolite was M A, followed by M 6, M 2, and then M 1. Except for the urinary excretion of M 4 there were no statistically significant differences in any of the pharmacokinetic parameters between the males and the females. The mean 24 h urinary recovery of M 4 was higher in the males than in the females (P< 0.05). However there were large inter-individual variations in the plasma concentrations and urinary excretion of DTZ and its metabolites with some parameters differing by more than 20-fold. In addition, O-desmethyl DTZ (M x) and N,O-didesmethyl DTZ (M B) were identified as two other major urinary metabolites.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalEuropean Journal of Drug Metabolism and Pharmacokinetics
Volume18
Issue number2
DOIs
StatePublished - Jun 1993

Keywords

  • Diltiazem
  • calcium antagonist
  • metabolism
  • pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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