title: Genetic polymorphism of CYP2C19 in a Jordanian population: influence of allele frequencies of CYP2C19*1 and CYP2C19*2 on the pharmacokinetic profile of lansoprazole.
abstract: To relate the pharmacokinetics of orally administered lansoprazole in healthy adult Jordanian men with CYP2C19 polymorphisms and to determine the percentage of CYP2C19 polymorphism in Jordanian population and the allelic frequency of CYP2C19*2 and CYP2C19*3. A total of 78 healthy Jordanian volunteers were included in this study from three different bioequivalence studies, one of these studies which included 26 volunteers was done on lansoprazole. Genotyping for CYP2C19*1, CYP2C19*2, CYP2C19*3 was done for all 78 volunteers, the data of genotyping of all subjects used for screening the frequency of different genotypes and the allelic frequency of different polymorphisms in healthy Jordanian men, the pharmacokinetics and genotyping data for the study of lansoprazole was matched and compared to investigate presence of statistical differences in pharmacokinetic parameters. In Jordanian subjects, the allele frequencies of the CYP2C19*2 and CYP2C19*3 mutation were 0.16 and 0, respectively. The concentration-time curves in the two groups [homozygote extensive metabolizer (homEM, n = 19) and heterozygote extensive metabolizer (homEM, n = 7)] groups were fitted to a non-compartment model. In the homEM and in the hetEM groups, the main kinetic parameters were as follows: T(max) (2.1875 ± 0.777) and (2.54 ± 1.87) h, C(max) (697.875 ± 335) and (833.58 ± 436.26) mg/l, t(1/2) (1.3 ± 0.43) and (2.38 ± 1.64) h, AUC((0→∞)) were (1,684.9 ± 888) and (3,609.8 ± 318) mg h l(-1), respectively. The Jordanian population showed similarities in CYP2C19 allele and genotype distribution pattern with Caucasians and Africans. CYP2C19 allele and poor metabolizer (PM) genotype frequencies in the Jordanian population are distinct from populations' from East Asia such as Japanese and Koreans. Although lower pharmacokinetic parameters were found in homEM compared to hetEM but there was no significant difference between the two groups (P < 0.05).
authors.affiliation: Faculty of Pharmacy, University of Jordan, Amman, 11942, Jordan.
authors.forename: Imad
authors.initials: I
authors.lastname: Zalloum
authors.forename: Nancy
authors.initials: N
authors.lastname: Hakooz
authors.forename: Tawfiq
authors.initials: T
authors.lastname: Arafat
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000493:pharmacokinetics*; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D003710:Demography; D005787:Gene Frequency / Q000235:genetics*; D005828:Genetics, Population; D060005:Genotyping Techniques; D006801:Humans; D007597:Jordan; D064747:Lansoprazole; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013997:Time Factors
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D064747:Lansoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19