Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism

I. Ieiri, Y. Kishimoto, H. Okochi, K. Momiyama, T. Morita, M. Kitano, T. Morisawa, Y. Fukushima, K. Nakagawa, J. Hasegawa, K. Otsubo, T. Ishizaki

Research output: Contribution to journalArticle

Abstract

Background: Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19. Aim: To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C19 genotypic status. Methods: Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n=5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner. Results: The relative values for the area under the serum concentration-time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively. Conclusion: The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen.

Original languageEnglish
Pages (from-to)485-492
Number of pages8
JournalCancer Chemotherapy and Pharmacology, Supplement
Volume49
Issue number7
Publication statusPublished - May 23 2002
Externally publishedYes

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Rabeprazole
Lansoprazole
Gastrins
Serum
Proton Pump Inhibitors
Area Under Curve
Helicobacter pylori
Pharmaceutical Preparations
Cytochrome P-450 CYP2C19
Healthy Volunteers
Pharmacology
Acids

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Cancer Research

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Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism. / Ieiri, I.; Kishimoto, Y.; Okochi, H.; Momiyama, K.; Morita, T.; Kitano, M.; Morisawa, T.; Fukushima, Y.; Nakagawa, K.; Hasegawa, J.; Otsubo, K.; Ishizaki, T.

In: Cancer Chemotherapy and Pharmacology, Supplement, Vol. 49, No. 7, 23.05.2002, p. 485-492.

Research output: Contribution to journalArticle

Ieiri, I, Kishimoto, Y, Okochi, H, Momiyama, K, Morita, T, Kitano, M, Morisawa, T, Fukushima, Y, Nakagawa, K, Hasegawa, J, Otsubo, K & Ishizaki, T 2002, 'Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism', Cancer Chemotherapy and Pharmacology, Supplement, vol. 49, no. 7, pp. 485-492.
Ieiri, I. ; Kishimoto, Y. ; Okochi, H. ; Momiyama, K. ; Morita, T. ; Kitano, M. ; Morisawa, T. ; Fukushima, Y. ; Nakagawa, K. ; Hasegawa, J. ; Otsubo, K. ; Ishizaki, T. / Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism. In: Cancer Chemotherapy and Pharmacology, Supplement. 2002 ; Vol. 49, No. 7. pp. 485-492.
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abstract = "Background: Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19. Aim: To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C19 genotypic status. Methods: Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n=5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner. Results: The relative values for the area under the serum concentration-time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively. Conclusion: The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen.",
author = "I. Ieiri and Y. Kishimoto and H. Okochi and K. Momiyama and T. Morita and M. Kitano and T. Morisawa and Y. Fukushima and K. Nakagawa and J. Hasegawa and K. Otsubo and T. Ishizaki",
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T1 - Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism

AU - Ieiri, I.

AU - Kishimoto, Y.

AU - Okochi, H.

AU - Momiyama, K.

AU - Morita, T.

AU - Kitano, M.

AU - Morisawa, T.

AU - Fukushima, Y.

AU - Nakagawa, K.

AU - Hasegawa, J.

AU - Otsubo, K.

AU - Ishizaki, T.

PY - 2002/5/23

Y1 - 2002/5/23

N2 - Background: Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19. Aim: To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C19 genotypic status. Methods: Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n=5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner. Results: The relative values for the area under the serum concentration-time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively. Conclusion: The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen.

AB - Background: Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19. Aim: To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C19 genotypic status. Methods: Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n=5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner. Results: The relative values for the area under the serum concentration-time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively. Conclusion: The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen.

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