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  • Title: Influence of CYP2C19 on the relationship between pharmacokinetics and intragastric pH of omeprazole administered by successive intravenous infusions in Chinese healthy volunteers.
    Author: Wang Y, Zhang H, Meng L, Wang M, Yuan H, Ou N, Zhang H, Li Z, Shi R.
    Journal: Eur J Clin Pharmacol; 2010 Jun; 66(6):563-9. PubMed ID: 20414645.
    Abstract:
    OBJECTIVES: To explore the effect of cytochrome P450 2C19 (CYP2C19) polymorphisms on the relationship between the pharmacokinetics and pharmacodynamics of omeprazole administered by intravenous successive infusions in Chinese healthy volunteers. METHODS: A total of 21 subjects [7 homozygous extensive metabolizers (homEMs), 9 heterozygous extensive metabolizers (hetEMs), 5 poor metabolizers (PMs)] received a 5-day course of omeprazole (40 mg) administered as a single dose daily during a 30-min period. Plasma concentrations were monitored by sampling at very short intervals for the first 8.5 h post-omeprazole administration and at 24 h post-administration, and intragastric pH was recorded on days 1 and 5. RESULTS: After a single dose, both the area under the plasma concentration-time curve (AUC) and peak concentration (C(max)) were higher in PMs than in EMs. Both the mean half-life (t((1/2))) and total clearance in PMs were significantly higher and lower than those in homEMs and EMs, respectively. Mean AUC and C(max) ratios in homEMs, hetEMs, and PMs were 1.0:1.1:1.4 and 1.0:1.0:1.1, respectively. Relative to the values determined after a single dose in EMs, after repeated doses, the intragastric pH, AUC, C(max), and t((1/2)) had increased significantly, while the total clearance had decreased significantly. Mean AUC and C(max) ratios in homEMs, hetEMs, and PMs were 1.4:1.4:1.5 and 1.2:1.2:1.3, respectively, compared to those of a single dose. The mean intragastric pH was significantly higher in PMs than in EMs after the fifth dose. CONCLUSIONS: There is a relationship between the pharmacokinetics and pharmacodynamics of omeprazole, with the latter depending in part on the duration of administration as evidenced by a higher AUC or C(max) and intragastric pH resulting from repeated dosing.
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