title: CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in healthy volunteers.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  These data suggest that CYP2C19 polymorphism is an important determinant of pantoprazole pharmacokinetics.
authors.affiliation: Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp 72, 70-111 Szczecin, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gawrońska-Szklarz
authors.forename: Urszula
authors.initials: U
authors.lastname: Adamiak-Giera
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Wyska
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kurzawski
authors.forename: Wanda
authors.initials: W
authors.lastname: Gornik
authors.forename: Maria
authors.initials: M
authors.lastname: Kaldonska
authors.forename: Marek
authors.initials: M
authors.lastname: Drozdzik
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001711:Biotransformation / Q000187:drug effects; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006207:Half-Life; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D000077402:Pantoprazole; D010641:Phenotype; D011044:Poland; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19