title: Variation in pharmacokinetics of omeprazole and its metabolites by gender and CYP2C19 genotype in Pakistani male and female subjects.
abstract: Pharmacokinetics (PK) variation of drugs in males and females may affect therapeutic effectiveness and safety. In current study the PK differences for omeprazole and its metabolites5-hydroxy-omeprazole and omeprazole-sulphone were evaluated in males and females. The current study also considered PK comparison of Pakistani subjects using the CYP2C19 genotype as variable. A single oral dose (40mg omeprazole), open-labeland, non-controlled clinical trial was arranged. Samples were quantified using reversed phase HPLC-UV method. CYP2C19 genotype of subjects was determined by tetra primer polymerization chain reaction (PCR) assay. There was a significant increase in Cmax (from 2 to 2.9μg/ml, p=0.004**), (from 6.67 to 8.74μg-hr/ml, p=0.05*) and elimination half-life (from 1.05 to 2.1 hr, p=0.0001*) of omeprazole in females compared with males. Cmax and of 5-hydroxy-omeprazole (0.0248* and 0.0001***, respectively) and omeprazole-sulphone (0.0001*** and 0.001**, respectively) was significantly higher in females than males when compared at 95% confidence interval. The Cmax and AUC of omeprazole showed a significant raise (p=0.01* and 0.04*, respectively) in Homz PMs (Homozygous Poor Metabolizers) compared with Homz EMs (Homozygous Extensive Metabolizers) and Htrz PMs (Heterozygous Poor Metabolizers) while Cmax and AUC of 5-hydroxy-omeprazolewas significantly higher (p=0.01* and 0.04*, respectively) in Homz EMs compared with Homz PMs and HtrzPMs. AUC of omeprazole was significantly higher in females while its elimination also took longer compared with males. AUC of omeprazole was significantly higher in Homz PMs indicating that CYP2C19* displayed genetically deficient metabolism in its homozygous state.
authors.affiliation: Kohat University of Science and Technology, Department of Pharmacy, Kohat, Pakistan.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Nazir
authors.affiliation: University of Peshawar, Peshawar, Department of Pharmacy, Peshawar, Pakistan.
authors.forename: Zafar
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: University of Swabi, Department of Pharmacy, Swabi, Pakistan.
authors.forename: Lateef
authors.initials: L
authors.lastname: Ahmad
authors.affiliation: Kohat University of Science and Technology, Department of Pharmacy, Kohat, Pakistan.
authors.forename: Sagheer
authors.initials: S
authors.lastname: Ahmad
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000378:metabolism; D000284:Administration, Oral; D019540:Area Under Curve; D001711:Biotransformation; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006900:Hydroxylation; D016014:Linear Models; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D010154:Pakistan; D010597:Pharmacogenetics; D010641:Phenotype; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012737:Sex Factors; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; C040450:omeprazole sulfone; C049963:5-hydroxymethylomeprazole; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole