Interethnic differences of PEPT2 (SLC15A2) polymorphism distribution and associations with cephalexin pharmacokinetics in healthy Asian subjects.

The aims of this study were to characterize the population frequency of PEPT2 ( SLC15A2) polymorphic variants in three Asian ethnic populations, namely Chinese, Malay and Asian Indian, and to investigate the associations of ethnicity (Chinese vs. Asian Indian), PEPT2 haplotype and cephalexin pharmac...

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Publicado en:European Journal of Clinical Pharmacology Vol. 65; no. 1; pp. 65 - 71
Autores principales: Liu R, Tang A, Tan Y, Limenta L, Lee E
Formato: research tables/charts Journal Article
Publicado: Springer Nature Jan2009
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jan2009
      vid: 65
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-008-0488-4
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        atl: Interethnic differences of PEPT2 (SLC15A2) polymorphism distribution and associations with cephalexin pharmacokinetics in healthy Asian subjects.
      aug:
        au:
          Liu R
          Tang A
          Tan Y
          Limenta L
          Lee E
        affil: Department of Pharmacology, Yong Loo Lin School of Medicine , National University of Singapore , Block MD11, Level 5, #05-09, Clinical Research Centre, 10 Medical Drive Singapore 117597 Singapore
      sug:
        subj:
          Cephalexin Pharmacokinetics
          Peptides Physiology
          Polymorphism, Genetic
          Adult
          Asians
          Cephalexin Administration and Dosage
          Cephalexin Therapeutic Use
          Chi Square Test
          China
          Confidence Intervals
          Data Analysis Software
          Ethnic Groups
          Female
          Funding Source
          Genotype
          Kidney Physiopathology
          Male
          Mann-Whitney U Test
          Membrane Transport Proteins
          Pharmacy and Pharmacology
          T-Tests
          Human
          Adult: 19-44 years
          Female
          Male
      ab: The aims of this study were to characterize the population frequency of PEPT2 ( SLC15A2) polymorphic variants in three Asian ethnic populations, namely Chinese, Malay and Asian Indian, and to investigate the associations of ethnicity (Chinese vs. Asian Indian), PEPT2 haplotype and cephalexin pharmacokinetics in healthy Asian subjects. PEPT2 polymorphisms were screened from a cohort of 96 Chinese, 96 Malay and 96 Asian Indian subjects. Cephalexin (1000 mg, orally) pharmacokinetics was characterized in an additional 15 Chinese and 15 Asian Indian healthy subjects. These 30 subjects were subsequently genotyped for their PEPT2 polymorphisms. In total, ten common single nucleotide polymorphisms (SNPs) were detected in the three populations, forming two PEPT2 haplotypes. There were significant ethnic differences in PEPT2 haplotype distribution: the frequencies of the *1 and *2 alleles were 0.307 and 0.693 in the Chinese population, 0.495 and 0.505 in the Malay population and 0.729 and 0.271 in Asian Indian population, respectively. The C max of cephalexin was significantly lower in the Chinese (29.80 ± 4.09 [mu]g ml-1) population than in the Asian Indian one (33.29 ± 4.97 [mu]g ml-1; P = 0.045). This difference could be explained by the higher average body weight of the Chinese population. There was no other significant difference in cephalexin pharmacokinetics between either ethnic or PEPT2 genotype groups. PEPT2 polymorphism distributions differ significantly between Chinese, Malay and Asian Indian populations. However, cephalexin pharmacokinetics is not meaningfully different between Chinese and Asian Indians. The association between the PEPT2 haplotype and cephalexin pharmacokinetics could not be confirmed, and future studies under better controlled conditions are needed.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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