Drug metabolism in the paediatric population and in the elderly

被引:50
作者
Benedetti, Margherita Strolin
Whomsley, Rhys
Canning, Michael
机构
[1] UCB Pharma, F-92003 Nanterre, France
[2] UCB Pharma, Chem Foriest, B-1420 Braine lAlleud, Belgium
关键词
D O I
10.1016/j.drudis.2007.06.011
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This review focuses on one of the key factors accounting for differences in drug/metabolite exposure in paediatric and elderly subjects compared with that of the adult population, that is, differences in drug metabolism (both qualitative and quantitative) and in particular differences due to changes in the activity and/or concentration of drug metabolizing enzymes. Important differences have been found in the paediatric population compared with adults for both phase I (e.g. CYP3A7 versus CYP3A4 and CYP1A2, reductive and hydrolytic enzymes) and phase 11 (e.g. glucuronosyltransferases) enzymes. In the elderly, some phase I enzymes (e.g. esterases) appear to be impaired. From the information collected thus far, it would appear that phase 11 reactions, though sometimes decreased, are not extensively affected by old age.
引用
收藏
页码:599 / 610
页数:12
相关论文
共 103 条
  • [31] AGE BUT NOT GENDER SELECTIVELY AFFECTS EXPRESSION OF INDIVIDUAL CYTOCHROME-P450 PROTEINS IN HUMAN LIVER
    GEORGE, J
    BYTH, K
    FARRELL, GC
    [J]. BIOCHEMICAL PHARMACOLOGY, 1995, 50 (05) : 727 - 730
  • [32] Pharmacokinetic and pharmacodynamic factors that can affect sensitivity to neurotoxic sequelae in elderly individuals
    Ginsberg, G
    Hattis, D
    Russ, A
    Sonawane, B
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 2005, 113 (09) : 1243 - 1249
  • [33] Developmental expression of cytochrome P450 enzymes in human liver
    Hakkola, J
    Tanaka, E
    Pelkonen, O
    [J]. PHARMACOLOGY & TOXICOLOGY, 1998, 82 (05): : 209 - 217
  • [34] HERD B, 1991, BRIT J CLIN PHARMACO, V32, P768
  • [35] Effects of age and sex on the disposition of retigabine
    Hermann, R
    Ferron, GM
    Erb, K
    Knebel, N
    Ruus, P
    Paul, J
    Richards, L
    Cnota, HP
    Troy, S
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 2003, 73 (01) : 61 - 70
  • [36] The ontogeny of human drug-metabolizing enzymes: Phase I oxidative enzymes
    Hines, RN
    McCarver, DG
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 300 (02) : 355 - 360
  • [37] Expression of the glutathione enzyme system of human colon mucosa by localisation, gender and age
    Hoensch, H.
    Peters, W. H. M.
    Roelofs, H. M. J.
    Kirch, W.
    [J]. CURRENT MEDICAL RESEARCH AND OPINION, 2006, 22 (06) : 1075 - 1083
  • [38] HEPATIC CYTOCHROME-P-4503A (CYP3A) ACTIVITY IN THE ELDERLY
    HUNT, CM
    WESTERKAM, WR
    STAVE, GM
    WILSON, JAP
    [J]. MECHANISMS OF AGEING AND DEVELOPMENT, 1992, 64 (1-2) : 189 - 199
  • [39] The effect of aging on the relationship between the cytochrome P4502C19 genotype and omeprazole pharmacokinetics
    Ishizawa, Y
    Yasui-Furukori, N
    Takahata, T
    Sasaki, M
    Tateishi, T
    [J]. CLINICAL PHARMACOKINETICS, 2005, 44 (11) : 1179 - 1189
  • [40] Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children
    Johnson, Trevor N.
    Rostami-Hodjegan, Amin
    Tucker, Geoffrey T.
    [J]. CLINICAL PHARMACOKINETICS, 2006, 45 (09) : 931 - 956