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, Rongshi Li, P. Farmer, G. A. Klassen

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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 1 1993

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Diltiazem
Pharmacokinetics
Oxides
Volunteers
Healthy Volunteers
High Pressure Liquid Chromatography
Urine

Keywords

  • Diltiazem
  • calcium antagonist
  • metabolism
  • pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Yeung, P. K. F., Prescott, C., Haddad, C., Montague, T. J., McGregor, C., Quilliam, M. A., ... Klassen, G. A. (1993). Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose. European Journal of Drug Metabolism and Pharmacokinetics, 18(2), 199-206. https://doi.org/10.1007/BF03188796

Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose. / Yeung, P. K.F.; Prescott, C.; Haddad, C.; Montague, T. J.; McGregor, C.; Quilliam, M. A.; Xei, M.; Li, Rongshi; Farmer, P.; Klassen, G. A.

In: European Journal of Drug Metabolism and Pharmacokinetics, Vol. 18, No. 2, 01.06.1993, p. 199-206.

Research output: Contribution to journalArticle

Yeung, PKF, Prescott, C, Haddad, C, Montague, TJ, McGregor, C, Quilliam, MA, Xei, M, Li, R, Farmer, P & Klassen, GA 1993, 'Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose', European Journal of Drug Metabolism and Pharmacokinetics, vol. 18, no. 2, pp. 199-206. https://doi.org/10.1007/BF03188796
Yeung, P. K.F. ; Prescott, C. ; Haddad, C. ; Montague, T. J. ; McGregor, C. ; Quilliam, M. A. ; Xei, M. ; Li, Rongshi ; Farmer, P. ; Klassen, G. A. / Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose. In: European Journal of Drug Metabolism and Pharmacokinetics. 1993 ; Vol. 18, No. 2. pp. 199-206.
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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.",
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AU - McGregor, C.

AU - Quilliam, M. A.

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AU - Li, Rongshi

AU - Farmer, P.

AU - Klassen, G. A.

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N2 - 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.

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