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Eur J Clin Pharmacol. 2012 Sep;68(9):1267-74. doi: 10.1007/s00228-012-1252-3. Epub 2012 Mar 15.

CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in healthy volunteers.

Author information

1
Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp 72, 70-111 Szczecin, Poland.

Abstract

OBJECTIVES:

Pantoprazole is metabolized by cytochrome P450 2 C19, which shows genetic polymorphism. The effect of CYP2C19 polymorphism on single-dose pharmacokinetics of oral pantoprazole in healthy volunteers was evaluated.

METHODS:

Pantoprazole pharmacokinetics was determined in 32 healthy volunteers after a 40-mg single oral dose of the drug.

RESULTS:

Carriers of CYP2C19*2/*2 (n = 2) were characterized by higher, starting from 3.5 h post dose, plasma concentrations of pantoprazole in comparison to wild-type (CYP2C19*1/*1, n = 6) volunteers. In subjects with CYP2C19*17/*17 genotype (n = 6) significantly lower plasma concentrations of the drug vs CYP2C19*1/*1 carriers, were observed from 3.0 h after oral pantoprazole administration. Carriers of CYP2C19*1/*17 (n = 6) and CYP2C19*2/*17 (n = 6) displayed concentration-time profiles comparable to wild-type subjects. CYP2C19*2/*2 volunteers showed a decrease in terminal elimination rate constant (λ(z)) by 83.3%, prolongation of terminal half-life (t(½)) by 572%, a rise in area under the concentration-time curve (AUC) and mean residence time (MRT) by 506% and 259% respectively. Heterozygotes, i.e.. CYP2C19*1/*2 vs CYP2C19*1/*1 were characterized by higher AUC (4.38 ± 1.00 mg·h/L vs 3.00 ± 1.02 mg·h/L, p < 0.05) and C(max) (2.13 ± 0.42 mg/L vs 1.61 ± 0.35 mg/L, p < 0.05) respectively. A significant reduction in MRT (3.83 ± 0.82 h vs 2.73 ± 0.23 h, p < 0.05) in carriers of CYP2C19*17/*17 vs CYP2C19*1/*1 genotypes was observed. Population modeling confirmed the influence of *1/*2, *2/*2, and *17/*17 genotypes on the pharmacokinetics of pantoprazole. The lowest population oral clearance was assessed in the carriers of genotype *2/*2 (3.68 L/h) and the highest value in subjects with genotype *17/*17 (31.13 L/h).

CONCLUSION:

These data suggest that CYP2C19 polymorphism is an important determinant of pantoprazole pharmacokinetics.

PMID:
22418828
PMCID:
PMC3419350
DOI:
10.1007/s00228-012-1252-3
[Indexed for MEDLINE]
Free PMC Article

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