Ticlopidine decreases the in vivo activity of CYP2C19 as measured by omeprazole metabolism

Tomonori Tateishi, Toshio Kumai, Minoru Watanabe, Hironori Nakura, Masami Tanaka, Shinichi Kobayashi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Aims. To examine the effect of ticlopidine administration on the activities CYP2C19 and CYP3 A in vivo using omeprazole as a model substrate. Methods. A single dose of 40 mg omeprazole was administered orally with or without ticlopidine (300 mg daily for 6 days) to six Japanese extensive metabolisers with respect to CYP2C19. Blood samples were taken for the measurement of plasma concentrations of omeprazole, 5-hydroxyomeprazole and omeprazole sulphone. Results. Ticlopidine administration increased omeprazole C(max) (1978 ± 859/3442 ± 569 (control phase/ticlopidine phase, nM)) and decreased the oral clearance of omeprazole (CL/F; 25.70 ± 16.17/10.76 ± 1.16 (control phase/ticlopidine phase, 1 h-1)) significantly. The 5-hydroxyomeprazole to omeprazole AUC ratio (0.817 ± 0.448/0.236 ± 0.053 (control phase/ticlopidine phase)) and the 5-hydroxyomeprazole to omeprazole sulphone AUC ratio (1.114 ± 0.782/0.256 ± 0.051 (control phase/ticlopidine phase)) were decreased significantly after ticloyidine administration. The decrease in omeprazole CL/F and the 5-hydroxyomeprazole to omeprazole AUC ratio correlated significantly with their respective absolute values when the drug was given alone. The decrease in CL/F following ticlopidine administration correlated with that in the 5-hydroxyomeprazole to omeprazole AUC ratio. Condusions. These findings suggest that ticlopidine inhibited the in vivo activity of CYP2C19, but not, or to a lesser extent CYP3 A4, and that the magnitude of inhibition by ticlopidine is related to the in vivo activity of CYP2C29 before inhibition.

Original languageEnglish
Pages (from-to)454-457
Number of pages4
JournalBritish Journal of Clinical Pharmacology
Volume47
Issue number4
DOIs
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Ticlopidine
Omeprazole
Area Under Curve
Cytochrome P-450 CYP2C19
5-hydroxymethylomeprazole

Keywords

  • CYP2C19
  • CYP3A
  • Drug interaction
  • Omeprazole
  • Ticlopidine

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Ticlopidine decreases the in vivo activity of CYP2C19 as measured by omeprazole metabolism. / Tateishi, Tomonori; Kumai, Toshio; Watanabe, Minoru; Nakura, Hironori; Tanaka, Masami; Kobayashi, Shinichi.

In: British Journal of Clinical Pharmacology, Vol. 47, No. 4, 1999, p. 454-457.

Research output: Contribution to journalArticle

Tateishi, Tomonori ; Kumai, Toshio ; Watanabe, Minoru ; Nakura, Hironori ; Tanaka, Masami ; Kobayashi, Shinichi. / Ticlopidine decreases the in vivo activity of CYP2C19 as measured by omeprazole metabolism. In: British Journal of Clinical Pharmacology. 1999 ; Vol. 47, No. 4. pp. 454-457.
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T1 - Ticlopidine decreases the in vivo activity of CYP2C19 as measured by omeprazole metabolism

AU - Tateishi, Tomonori

AU - Kumai, Toshio

AU - Watanabe, Minoru

AU - Nakura, Hironori

AU - Tanaka, Masami

AU - Kobayashi, Shinichi

PY - 1999

Y1 - 1999

N2 - Aims. To examine the effect of ticlopidine administration on the activities CYP2C19 and CYP3 A in vivo using omeprazole as a model substrate. Methods. A single dose of 40 mg omeprazole was administered orally with or without ticlopidine (300 mg daily for 6 days) to six Japanese extensive metabolisers with respect to CYP2C19. Blood samples were taken for the measurement of plasma concentrations of omeprazole, 5-hydroxyomeprazole and omeprazole sulphone. Results. Ticlopidine administration increased omeprazole C(max) (1978 ± 859/3442 ± 569 (control phase/ticlopidine phase, nM)) and decreased the oral clearance of omeprazole (CL/F; 25.70 ± 16.17/10.76 ± 1.16 (control phase/ticlopidine phase, 1 h-1)) significantly. The 5-hydroxyomeprazole to omeprazole AUC ratio (0.817 ± 0.448/0.236 ± 0.053 (control phase/ticlopidine phase)) and the 5-hydroxyomeprazole to omeprazole sulphone AUC ratio (1.114 ± 0.782/0.256 ± 0.051 (control phase/ticlopidine phase)) were decreased significantly after ticloyidine administration. The decrease in omeprazole CL/F and the 5-hydroxyomeprazole to omeprazole AUC ratio correlated significantly with their respective absolute values when the drug was given alone. The decrease in CL/F following ticlopidine administration correlated with that in the 5-hydroxyomeprazole to omeprazole AUC ratio. Condusions. These findings suggest that ticlopidine inhibited the in vivo activity of CYP2C19, but not, or to a lesser extent CYP3 A4, and that the magnitude of inhibition by ticlopidine is related to the in vivo activity of CYP2C29 before inhibition.

AB - Aims. To examine the effect of ticlopidine administration on the activities CYP2C19 and CYP3 A in vivo using omeprazole as a model substrate. Methods. A single dose of 40 mg omeprazole was administered orally with or without ticlopidine (300 mg daily for 6 days) to six Japanese extensive metabolisers with respect to CYP2C19. Blood samples were taken for the measurement of plasma concentrations of omeprazole, 5-hydroxyomeprazole and omeprazole sulphone. Results. Ticlopidine administration increased omeprazole C(max) (1978 ± 859/3442 ± 569 (control phase/ticlopidine phase, nM)) and decreased the oral clearance of omeprazole (CL/F; 25.70 ± 16.17/10.76 ± 1.16 (control phase/ticlopidine phase, 1 h-1)) significantly. The 5-hydroxyomeprazole to omeprazole AUC ratio (0.817 ± 0.448/0.236 ± 0.053 (control phase/ticlopidine phase)) and the 5-hydroxyomeprazole to omeprazole sulphone AUC ratio (1.114 ± 0.782/0.256 ± 0.051 (control phase/ticlopidine phase)) were decreased significantly after ticloyidine administration. The decrease in omeprazole CL/F and the 5-hydroxyomeprazole to omeprazole AUC ratio correlated significantly with their respective absolute values when the drug was given alone. The decrease in CL/F following ticlopidine administration correlated with that in the 5-hydroxyomeprazole to omeprazole AUC ratio. Condusions. These findings suggest that ticlopidine inhibited the in vivo activity of CYP2C19, but not, or to a lesser extent CYP3 A4, and that the magnitude of inhibition by ticlopidine is related to the in vivo activity of CYP2C29 before inhibition.

KW - CYP2C19

KW - CYP3A

KW - Drug interaction

KW - Omeprazole

KW - Ticlopidine

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