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  • Title: 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.
    Author: Ieiri I, Kishimoto Y, Okochi H, Momiyama K, Morita T, Kitano M, Morisawa T, Fukushima Y, Nakagawa K, Hasegawa J, Otsubo K, Ishizaki T.
    Journal: Eur J Clin Pharmacol; 2001 Sep; 57(6-7):485-92. PubMed ID: 11699613.
    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 CYP2C/9 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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