Liver function and phase I drug metabolism in the elderly: A paradox

Drugs and Aging

Volumn 18, Issue 11, 2001, Pages 837-851

  Schmucker, Douglas L ^a,b  

^a SAN FRANCISCO VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450; UNSPECIFIC MONOOXYGENASE;

AGED; ANIMAL EXPERIMENT; DRUG CLEARANCE; DRUG METABOLISM; DRUG OXIDATION; ENZYME ACTIVITY; ENZYME DEFICIENCY; ENZYME INDUCTION; FIRST PASS EFFECT; HUMAN; LIVER BLOOD FLOW; LIVER FUNCTION; LIVER WEIGHT; MALE; MEMBRANE FLUIDITY; NONHUMAN; PHARMACOKINETICS; PRIORITY JOURNAL; RAT; REVIEW;

EID: 0035695389     PISSN: 1170229X     EISSN: None     Source Type: Journal    
DOI: 10.2165/00002512-200118110-00005     Document Type: Review

References (126)

1. Aging in the third millenium
2. Clinical trials in the elderly: Should we do more?
3. The trials and tribulations of clinical trials in the elderly
4. Centers for Disease Control: Co-morbidity of chronic conditions and disability among older persons: United States
5. Reporting of age data in clinical trials of arthritis
6. Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons
7. Detailed diagnoses and procedures: National Hospital Discharge Survey, 1989
8. Cancer in the elderly
9. Representation of older patients in cancer treatment trials
10. Are the elderly underrepresented in clinical drug trials?
11. Prescribing for the elderly: Part I. Sensitivity of the elderly to adverse drug reactions
12. Hospital admissions due to adverse drug reactions: A comparative study from Jerusalem and Berlin
13. Adverse reactions to prescribed drugs in the elderly: A multi-center investigation
14. Characterization of geriatric drag-related hospital re-admissions
15. The ambiguous relation between aging and adverse drug reactions
16. Management of drug therapy in the elderly
17. Anticonvulsant therapy in the elderly: A need for placebo controlled trials
18. Clinical pharmacology in an aging population
19. Research challenges, a new drug development, preclinical and clinical trials in the aging population
20. Age-related changes in drug disposition
21. Age-related changes in drug disposition: An update
22. Aging and drug disposition
23. Aging and drug disposition
24. Liver disease in the elderly
25. Drug dosage in the elderly. Is it rational?
26. Aging and the liver: An update
27. Liver diseases
28. The formation of enlarged and giant mitochondria in the aging process of human hepatic cells
29. Some morphological and biochemical results on liver ageing, especially regarding connective tissue
30. Protein metabolism in the elderly
31. The effect of age upon liver volume and apparent liver blood flow in healthy man
32. Galactose elimination capacity and liver volume in aging man
33. Disposition of antipyrine and phenytoin correlated with age and liver volume in man
34. Antipyrine disposition and liver size in the elderly
35. Aging and the liver
36. Polyploid cell production in normal adult rat liver
37. Bromsulfophthalein storage capacity of rat hepatocytes separated into ploidy classes by centrifugal elutriation
38. A flow cytofluorometric study of age-dependent ploidy class changes in mouse hepatocyte nuclei
39. Euploidization of human hepatocytes from donors of different ages and both sexes compared with those from cases of Werner's syndrome and progeria
40. Human hepatocyte polyploidization kinetics in the course of life cycle
41. Image processing in pathology. IV. Age-dependent changes in morphometric features of liver cell nuclei in biopsies
42. Hepatic cells of the aged
43. On the role of hepatic cell ploidy changes in liver function with age following partial hepatectomy
44. Stereological analysis of hepatic fine structure in the Fischer 344 rat. Influence of sublobular location and animal age
45. Lysosomal activity in the aging liver. II. Morphometry of acid phosphatase positive dense bodies
46. Stereological analysis of liver parenchymal cells from young and old rats
47. The aging rat liver as revealed by electron microscopic morphometry. I. Basic parameters
48. Age changes in the livers of Costa Ricans
49. Age-related alteration in the size of human hepatocytes. A study of mononuclear and binucleate cells
50. The hepatocyte: Development, differentiation and ageing
51. Ageing has no effect on the volume density of hepatocytes, reticuloendothelial cells or the extracellular space on livers of female Sprague-Dawley rats
52. Hepatocyte fine structure during maturation and senescence
53. Fine structural analysis of lipofuscin in various tissues of rats of different ages
54. Changes in lysosomes during aging of parenchymal liver cells
55. Lysosomal enzyme activities in parenchymal and nonparenchymal liver cells isolated from young adult and old rats
56. Rat liver lysosomal enzymes: Effects of animal age and phenobarbital
57. Drug-induced changes in the liver endoplasmic reticulum: Association with drug-metabolizing enzymes
58. Age-related changes in the hepatic endoplasmic reticulum: A quantitative analysis
59. Effects of aging and phenobarbital on the rat liver microsomal drug-metabolizing system
60. The influence of 'essential' phospholipids (EPL) on phase-I and phase-II reactions and on the glutathione status in the liver of aging rats
61. Age-dependent alterations in the physicochemical properties of rat liver microsomes
62. Coming of age
63. Hepatic drug metabolism in the elderly
64. Aging in liver and gastrointestinal tract
65. Alterations in the liver with ageing
66. Portal blood velocity and flow in aging man
67. Total and functional hepatic blood flow decrease in parallel with ageing
68. Age-related changes in the gastrointestinal system
69. Physiologic changes in old age: Relation to altered drug disposition
70. Hepatic drug metabolism and ageing
71. Age-related changes in hepatic function. Implications for drug therapy
72. Effect of age on liver function
73. Effect of age on liver function with particular reference to bromsulfophthalein excretion
74. Laboratory values in fit aging individuals -sexagenarians through centenarians
75. Kinetics of hepatic amino-nitrogen conversion in ageing man
76. Influence of age and sex on 19 blood variables in healthy subjects
77. Effect of aging on the hepatobiliary transport of dimeric immunoglobulin A in the male Fischer rat
78. Influence of age on secretion of cholesterol and synthesis of bile acids by the liver
79. Cardiovascular risk factors in the elderly
80. Influence of age on plasma low density lipoprotein metabolism in man
81. Influence of age on hepatic uptake of HDL-1-cholesterol in male Wistar rats with bile duct cannulation
82. In vitro synthesis of microsomal protein and albumin in young and old rats
83. Age-related changes in the synthesis of individual liver-specific proteins
84. Age-related changes in protein binding of drugs: Implications for therapy
85. Liver resection in the aged (seventy years or older) with hepatocellular carcinoma
86. Influence of age on results of resection of hepatocellular carcinoma
87. Hepatic resection in the elderly
88. Synthesis of RNA, protein and DNA in the livers of normal and hypophysectomized rats after partial hepatectomy
89. Effect of phenobarbital on electron transport system, oxidation and reduction of drugs in liver microsomes of rats of different age
90. Age-related changes in liver drug metabolism: Structure vs function
91. Influence of ageing and induction of rat liver and kidney microsomal mixed function oxidase systems
92. Induction of the hepatic cytochrome P450-dependent monooxygenase system in young and geriatric rats
93. The effect of aging on the kinetic profile of rat liver microsomal NADPH cytochrome c reductase
94. Age-dependent alterations in rat liver microsomal NADPH cytochrome c (P-450) reductase: A qualitative and quantitative analysis
95. Aging affects the regulation of preferentially expressed liver proteins in male Fischer 344 rats
96. Comparison of the hepatic mixed function oxidase system of young, adult and old non-human primates (Macaca nemestrina)
97. The effects of aging on the hepatic microsomal mixed function oxidase system of male and female monkeys
98. Effects of aging on the properties of rhesus monkey liver microsomal NADPH cytochrome c (P-450) reductase
99. Hepatic microsomal monooxygenase and A20 reductase activities in ageing Fischer 344 rats: Importance of sex difference for ageing studies
100. Age-related alterations in the activities of drug-metabolizing enzymes and contents of sex-specific forms of cytochrome P-450 in liver microsomes from male and female rats
101. Does aging compromise hepatic microsomal monooxygenase activity?
102. Influence of sex and oral contraceptives on antipyrine metabolite formation
103. Disposition of chlordiazepoxide: Sex differences and effects of oral contraceptives
104. Desmethyldiazepam kinetics in the elderly after oral prazepam
105. Diazepam disposition determinants
106. Cytochrome P-450 monooxygenase activities in human and rat liver microsomes
107. Lack of aging effect on human microsomal monooxygenase enzyme activities and on inactivation pathways for reactive metabolic intermediates
108. The effect of age on pathways of drug metabolism in human liver
109. Hepatic drug metabolism and aging
110. The effect of age upon the affinity of microsomal monooxygenase enzymes for substrate in human liver
111. Influence of liver disease and environmental factors on hepatic monooxygenase activity in vitro
112. Effect of age on tests of intestinal and hepatic function in healthy humans
113. Quantitative liver function in the elderly assessed by galactose elimination capacity, aminopyrine demethylation and caffeine clearance
114. Influence of age, frailty and liver function on the pharmacokinetics of brofaromine
115. The effect of age and sex on metabolism and urinary excretion of antipyrine
116. Age but not gender selectively affects expression of individual cytochrome P450 proteins in human liver
117. Age and cytochrome P450-linked drug metabolism in humans: An analysis of 26 subjects with equal histopathologic conditions
118. Effects of age and gender on in vitro properties of human liver microsomal monooxygenases
119. Hepatic cytochrome P-4503A (CYP3A) activity in the elderly
120. Effect of age and gender on the activity of human hepatic CYP3A
121. Interindividual variability in catalytic activity and immunoreactivity of three major human liver cytochrome P450 isozymes
122. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: Studies with liver microsomes of 30 Japanese and 30 Caucasians