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Drugs & Aging
Published in: Drugs & Aging 11/2001

01-11-2001 | Review Article

Liver Function and Phase I Drug Metabolism in the Elderly

A Paradox

Author: Douglas L. Schmucker

Published in: Drugs & Aging | Issue 11/2001

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Abstract

Aging is accompanied by marked changes in the physiology of many organs, as well as in their constituent cells. These nonpathological alterations in structure and/or function may affect normal physiological processes in the elderly (individuals >65 years), for example drug disposition. The liver plays a major role in drug clearance and aging has been reported to diminish this hepatic capacity, particularly the clearance of drugs that undergo mandatory oxidation by the microsomal cytochrome P450-dependent mono-oxygenase systems. Liver volume and blood flow decline with age in humans and, no doubt, this contributes to the diminished clearance of drugs that exhibit first-pass kinetic profiles.
Changes in liver morphology with aging that have been described in rodents are limited to the hepatocytes, for example accumulation of dense bodies and loss of smooth surfaced endoplasmic reticulum. There is no evidence that the increase in intracellular lipofuscin adversely affects hepatocyte functions. A number of studies have documented significant age-related declines in the amounts, specific activities and rates of induction of liver microsomal mono-oxygenases in inbred male rats.
On the basis of a variety of clinical tests, most liver functions in humans appear to be well preserved. The most remarkable characteristic of liver function in the elderly is the increase in interindividual variability, a feature that may obscure age-related differences. Most in vitro studies using nonhuman primate or human liver tissue did not detect age-related deficiencies in cytochrome P450-dependent microsomal mono-oxygenases. On the other hand, there have been recent reports of age-related, but not gender-related, declines in the in vitro activities of several human liver mono-oxygenases, for example the cytochrome P450 isoform CYP3A. Nevertheless, reduced liver volume and blood flow in the elderly permit the reconciliation of: (i) the in vivo clinical pharmacokinetic data indicative of reduced hepatic drug clearance; and (ii) the absence of significant age-related declines in the amounts or in vitro activities of liver microsomal mono-oxygenases.
Literature
1.
2.
Cameron HJ, Williams BO. Clinical trials in the elderly: should we do more? Drugs Aging 1996; 9: 307–10PubMedCrossRef
3.
Curb JD. The trials and tribulations of clinical trials in the elderly. J Am Geriatr Soc 1994; 42: 682–3PubMed
4.
Centers for Disease Control: Co-morbidity of chronic conditions and disability among older persons: United States. JAMA 1990; 263: 209–10
5.
Rochon PA, Fortin PR, Dear KB, et al. Reporting of age data in clinical trials of arthritis. Arch Intern Med 1993; 153: 243–8PubMedCrossRef
6.
Griffin MR, Ray WA, Schaffner W. Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Ann Intern Med 1988; 109: 359–63PubMed
7.
Graves EJ. Detailed diagnoses and procedures: National Hospital Discharge Survey, 1989. Vital Health Stat 13 1991 Sep; (108): 1–236
8.
Byrne A, Carney DN. Cancer in the elderly. Curr Probl Cancer 1993; 3: 151–5
9.
Trimble EL, Carter CL, Cain D, et al. Representation of older patients in cancer treatment trials. Cancer 1994; 74: 2208–14PubMedCrossRef
10.
Schmucker DL, Vesell ES. Are the elderly underrepresented in clinical drug trials? J Clin Pharmacol 1999; 39: 1103–8PubMed
11.
Food and Drag Administration: Annual Adverse Drag Experience Reports. Springfield (VA): US Department of Commerce, National Technical Information Service, 1991
12.
Nolan L, O’Mallet K. Prescribing for the elderly: Part I. Sensitivity of the elderly to adverse drag reactions. J Am Geriatr Soc 1988; 36: 142–9PubMed
13.
Levy M, Kewitz H, Altwein W, et al. Hospital admissions due to adverse drug reactions: a comparative study from Jerusalem and Berlin. Eur J Clin Pharmacol 1980; 17: 25–31PubMedCrossRef
14.
Williamson J, Chopin J. Adverse reactions to prescribed drags in the elderly: a multi-center investigation. Age Ageing 1980; 9: 73–80PubMedCrossRef
15.
Bero LA, Lipton HL, Bird JA. Characterization of geriatric drug-related hospital re-admissions. Med Care 1991; 29: 989–1000PubMedCrossRef
16.
Gurwitz JH, Avorn J. The ambiguous relation between aging and adverse drug reactions. Ann Intern Med 1991; 114: 956–66PubMed
17.
Montamat SC, Cusack BJ, Vestal RE. Management of drag therapy in the elderly. N Engl J Med 1989; 321: 303–9PubMedCrossRef
18.
Cameron H, Macphee GJ. Anticonvulsant therapy in the elderly: aneed forplacebo controlled trials. Epilepsy Res 1995; 21: 149–57PubMedCrossRef
19.
American Federation for Aging Research, Alliance for Aging Research. Putting aging on hold: delaying the diseases of old age. An official report to the White House Conference on Aging; 1995 Mar; Washington, DC
20.
Abrams WB, Beers MH. Clinical pharmacology in an aging population. Clin Pharmacol Ther 1998; 63: 281–4PubMedCrossRef
21.
Abernathy DR. Research challenges, a new drug development, preclinical and clinical trials in the aging population. Drug Saf 1990; 5Suppl. 1: 71–4CrossRef
22.
Schmucker DL. Age-related changes in drag disposition. Pharmacol Rev 1978; 30: 445–56PubMed
23.
Schmucker DL. Age-related changes in drug disposition: an update. Pharmacol Rev 1985; 37: 133–48PubMed
24.
Schmucker DL. Aging and drug disposition. Rev Biol Res Aging 1985; 2: 465–501
25.
Schmucker DL, Lonergon T. Aging and drug disposition. Rev Biol Res Aging 1987; 3: 509–35
26.
O’Mahony MS, Schmucker DL. Liver disease in the elderly. Semin Gastrointest Dis 1994; 5: 197–206PubMed
27.
Tumheim K. Drug dosage in the elderly. Is it rational? Drugs Aging 1998; 13: 357–79
28.
Schmucker DL. Aging and the liver: an update. J Gerontol 1998; 53A: B315–20CrossRef
29.
Varanasi RV, Varanasi SC, Howell CD. Liver diseases. Clin Geriatr Med 1999; 15: 559–70PubMed
30.
Andrew W. The anatomy of aging in man and animals. New York: Grane and Stratton, 1971
31.
Sato T, Tauchi H. The formation of enlarged and giant mitochondria in the aging process of human hepatic cells. Acta Pathol Jpn 1975; 25: 403–12PubMed
32.
Lindner J, Grasedyck K, Bittmann S, et al. Some morphological and biochemical results on liver ageing, especially regarding connective tissue. In: Platt D, editor. Liver and ageing: Proceedings of the 4th International Giessener Symposium on Experimental Gerontology. Stuttgart: FK Schattauer Verlag, 1977: 23–42
33.
Munro HN, Young VR. Protein metabolism in the elderly. Postgrad Med 1978; 63: 143–8PubMed
34.
Wynne H, Cope LH, Mutch W, et al. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology 1988; 9: 297–301CrossRef
35.
Marchesini G, Bua V, Brunori A, et al. Galactose elimination capacity and liver volume in aging man. Hepatology 1988; 8: 1079–83PubMedCrossRef
36.
Bach B, Hansen JM, Kampmann JP, et al. Disposition of antipyrine and phenytoin correlated with age and liver volume in man. Clin Pharmacokinet 1981; 6: 389–96PubMedCrossRef
37.
Swift CG, Homeida M, Halliwell M, et al. Antipyrine disposition and liver size in the elderly. Eur J Clin Pharmacol 1978; 14: 149–52PubMedCrossRef
38.
Popper H. Aging and the liver. In: Popper H, Schaffner F, editors. Progress in liver disease. Vol. III. Orlando (FL): Grane and Stratton, 1986: 659–683
39.
40.
Van Bezooijen CF, Bukvic SJ, Sleyster EC. Bromsulfophthalein storage capacity of rat hepatocytes separated into ploidy classes by centrifugal elutriation. In: van Bezooijen CF, editor. Pharmacological, morphological and physiological aspects of liver ageing. Rijswijk: EURAGE, 1983: 115–120
41.
Ohtsubo K, Nomaguchi TA. A flow cytofluorometric study of age-dependent ploidy class changes in mouse hepatocyte nuclei. Mech Ageing Dev 1986; 36: 125–31PubMedCrossRef
42.
Gahan PB, Middleton J. Euploidization of human hepatocytes from donors of different ages and both sexes compared with those from cases of Werner’s syndrome and progeria. Exp Gerontol 1984; 19: 355–8PubMedCrossRef
43.
Kudryavtsev BN, Kudryavtseva MV, Sakuta GA, et al. Human hepatocyte polyploidization kinetics in the course of life cycle. Virchows Arch B Cell Pathol 1993; 64: 387–93CrossRef
44.
Barz H, Kunze KD, Voss K. Image processing in pathology. IV. Age-dependent changes in morphometric features of liver cell nuclei in biopsies. Exp Pathol 1977; 14: 55–64
45.
Tauchi H, Sato T. Hepatic cells of the aged. In: Kitani K, editor. The liver and aging -1978. Amsterdam: Elsevier-North Holland, 1978: 3–19
46.
Van Bezooijen CF, DeLeeuw-Israel, F, et al. On the role of hepatic cell ploidy changes in liver function with age following partial hepatectomy. Mech Ageing Dev 1972; 1: 351–8CrossRef
47.
Schmucker DL, Mooney J, Jones AL. Stereological analysis of hepatic fine structure in the Fischer 344 rat. Influence of sublobular location and animal age. J Cell Biol 1978; 78: 319–37PubMedCrossRef
48.
DePriester W, van Manen R, Knook DL. Lysosomal activity in the aging liver. II. Morphometry of acid phosphatase positive dense bodies. Mech Ageing Dev 1984; 26: 205–16CrossRef
49.
Meihuizen SP, Blansjaar N. Stereological analysis of liver parenchymal cells from young and old rats. Mech Ageing Dev 1980; 13: 111–8PubMedCrossRef
50.
Pieri C, ZS-Nagy I, Mazzufferi G, et al. The aging rat liver as revealed by electron microscopic morphometry. I. Basic parameters. Exp Gerontol 1975; 10: 291–304PubMedCrossRef
51.
Sato T, Cesoedes RF, Goyenaga PH, et al. Age changes in the livers of Costa Ricans. Mech Ageing Dev 1979; 11: 171–8PubMedCrossRef
52.
Watanabe T, Tanaka Y. Age-related alteration in the size of human hepatocytes. A study of mononuclear and binucleate cells. Virchows Arch B Cell Pathol 1982; 39: 9–20CrossRef
53.
David H. The hepatocyte: development, differentiation and ageing. Exp Pathol Suppl 1985; 11: 1–148PubMed
54.
Martin G, Sewell RB, Yeomans ND, et al. Ageing has no effect on the volume density of hepatocytes, reticuloendothelial cells or the extracellular space on livers of female Sprague-Dawley rats. Clin Exp Pharmacol Physiol 1992; 19: 537–9PubMedCrossRef
55.
Schmucker DL. Hepatocyte fine structure during maturation and senescence. J Electron Microsc Tech 1990; 14: 106–25PubMedCrossRef
56.
Ikeda H, Tauchi H, Sato T. Fine structural analysis of lipofuscin in various tissues of rats of different ages. Mech Ageing Dev 1985; 33: 77–93PubMedCrossRef
57.
Knook DL, Sleyster EC, van Noord MJ. Changes in lysosomes during aging of parenchymal liver cells. Adv Exp Med Biol 1975; 53: 155–69PubMedCrossRef
58.
Knook DL, Sleyster EC. Lysosomal enzyme activities in parenchymal and nonparenchymal liver cells isolated from young adult and old rats. Mech Ageing Dev 1976; 5: 389–97PubMedCrossRef
59.
Schmucker DL, Wang, RK. Rat liver lysosomal enzymes: effects of animal age and phenobarbital. Age 1979; 2: 93–6CrossRef
60.
Remmer H, Merker HJ. Drug-induced changes in the liver endoplasmic reticulum: association with drug-metabolizing enzymes. Science 1963; 142: 1657–8PubMedCrossRef
61.
Schmucker DL, Mooney JS, Jones AL. Age-related changes in the hepatic endoplasmic reticulum: a quantitative analysis. Science 1977; 197: 1005–8CrossRef
62.
Schmucker DL, Wang RK. Effects of aging and phenobarbital on the rat liver microsomal drug-metabolizing system. Mech Ageing Dev 1981; 15: 189–202PubMedCrossRef
63.
Klinger W, Muller D, Kleeberg U, et al. The influence of’ essential’ phospholipids (EPL) on phase-I and phase-II reactions and on the glutathione status in the liver of aging rats. Exp Pathol 1991; 41: 151–6PubMedCrossRef
64.
Schmucker DL, Vessey DA, Wang RK, et al. Age-dependent alterations in the physicochemical properties of rat liver microsomes. Mech Ageing Dev 1984; 27: 207–17PubMedCrossRef
65.
66.
67.
Bianchi L, Holt P, James OFW, et al. Aging in liver and gastrointestinal tract. Falk Symposium Series 47. Lancaster: MTP Press, 1988
68.
Woodhouse KW, Yelland C, James, OFW. The liver: metabolism and ageing. Topics in aging research in Europe. Vol. 13. Rijswijk: EURAGE, 1989
69.
Mooney H, Roberts R, Cooksley WG, et al. Alterations in the liver with ageing. Clin Gastroenterol 1985; 14: 757–71PubMed
70.
Zoli M, Iervese T, Abbati S, et al. Portal blood velocity and flow in aging man. Gerontology 1989; 35: 61–5PubMedCrossRef
71.
Zoli M, Magalotti D, Bianchi G, et al. Total and functional hepatic blood flow decrease in parallel with ageing. Age Ageing 1999; 28: 29–33PubMedCrossRef
72.
Iber FL, Murphy PA, Connor ES. Age-related changes in the gastrointestinal system. Drugs Aging 1994; 5: 34–48PubMedCrossRef
73.
Greenblatt DJ, Divoll M, Abernathy DR, et al. Physiologic changes in old age: relation to altered drug disposition. J Am Geriatr Soc 1982; 30 Suppl.: S6–10PubMed
74.
Woodhouse KW, James OFW. Hepatic drug metabolism and ageing. Br Med Bull 1990; 46: 22–35PubMed
75.
Woodhouse KW, Wynne HA. Age-related changes in hepatic function. Implications for drug therapy. Drugs Aging 1992; 2: 243–55PubMedCrossRef
76.
Thompson EN. Effect of age on liver function. In: Platt D, editor. Liver and ageing. Proceedings of the 4th International Giessener Symposium on Experimental Gerontology. Stuttgart: FK Schattauer Verlag, 1977: 115–126
77.
Thompson EN, Williams R. Effect of age on liver function with particular reference to bromsulfophthalein excretion. Gut 1965; 6: 266–9PubMedCrossRef
78.
Tietz NW, Shuey DF, Wekstein DR. Laboratory values in fit aging individuals -sexagenarians through centenarians. Clin Chem 1992; 38: 1167–85PubMed
79.
Fabri A, Marchesini G, Bianchi G, et al. Kinetics of hepatic amino-nitrogen conversion in ageing man. Liver 1994; 14: 288–94
80.
Bohnen N, Degenaar CP, Jolies J. Influence of age and sex on 19 blood variables in healthy subjects. Z Gerontol 1992; 25: 339–45PubMed
81.
Schmucker DL, Gilbert R, Jones AL, et al. Effect of aging on the hepatobiliary transport of dimeric immunoglobulin A in the male Fischer rat. Gastroenterology 1985; 88: 436–43PubMed
82.
Einarsson K, Nilsell K, Leijd B. Influence of age on secretion of cholesterol and synthesis of bile acids by the liver. N Engl J Med 1985; 313: 277–82PubMedCrossRef
83.
Castelli WP, Wilson WF, Levy D, et al. Cardiovascular risk factors in the elderly. Am J Cardiol 1989; 63: H12–9CrossRef
84.
Ericsson S, Angelin B, Berglund L, et al. Influence of age on plasma low density lipoprotein metabolism in man. In: Kitani K, editor. Liver and Aging -1990. Amsterdam: Excerpta Medica, 1991: 295–304
85.
Bravo E, Pignatelli E, Masella R, et al. Influence of age on hepatic uptake of HDL-1-cholesterol in male Wistar rats with bile duct cannulation. J Biochem (Tokyo) 1994; 115: 833–6
86.
Chen JC, Ove P, Lansing A. In vitro synthesis of microsomal protein and albumin in young and old rats. Biochim Biophys Acta 1973; 312: 598–607PubMedCrossRef
87.
Horbach GJ, van Bezooijen CF, Knook DL. Age-related changes in the synthesis of individual liver-specific proteins. Rev Biol Res in Aging 1987; 3: 485–94
88.
Grandison MK, Boudinot FD. Age-related changes in protein binding of drugs: implications for therapy. Clin Pharmacokinet 2000; 38: 271–90PubMedCrossRef
89.
Nagasue N, Chang Y, Takewmoto Y, et al. Liver resection in the aged (seventy years or older) with hepatocellular carcinoma. Surgery 1993; 113: 148–54PubMed
90.
Chen M, Hwang T, Jeng L, et al. Influence of age on results of resection of hepatocellular carcinoma. Eur J Surg 1991; 157: 591–3PubMed
91.
92.
Rabes HM, Breandle H. Synthesis of RNA, protein and DNA in the livers of normal and hypophysectomized rats after partial hepatectomy. Cancer Res 1969; 29: 817–22PubMed
93.
Kato R, Takanaka A. Effect of phenobarbital on electron transport system, oxidation and reduction of drugs in liver microsomes of rats of different age. J Biochem (Tokyo) 1968; 63: 406–8
94.
Schmucker DL, Wang RK. Age-related changes in liver drug metabolism: structure vs function. Proc Soc Exp Biol Med 1980; 165: 178–97PubMed
95.
McMartin DN, O’Connor JA, Fasco MJ, et al. Influence of ageing and induction of rat liver and kidney microsomal mixed function oxidase systems. Toxicol Appl Pharmacol 1980; 54: 411–9PubMedCrossRef
96.
Kao J, Hudson P. Induction of the hepatic cytochrome P450-dependent monooxygenase system in young and geriatric rats. Biochem Pharmacol 1980; 29: 1191–4PubMedCrossRef
97.
Schmucker DL, Wang RK. The effect of aging on the kinetic profile of rat liver microsomal NADPH cytochrome c reductase. Exp Gerontol 1984; 18: 313–21CrossRef
98.
Schmucker DL, Wang RK. Age-dependent alterations in rat liver microsomal NADPH cytochrome c (P-450) reductase: a qualitative and quantitative analysis. Mech Ageing Dev 1983; 21: 137–56PubMedCrossRef
99.
Van Bezooijen RL, Wang RK, Lechner MC, et al. Aging affects the regulation of preferentially expressed liver proteins in male Fischer 344 rats. Exp Gerontol 1994; 29: 186–96
100.
Sutter MA, Wood WG, Williamson LS, et al. Comparison of the hepatic mixed function oxidase system of young, adult and old non-human primates (Macaca nemestrina). Biochem Pharmacol 1985; 34: 2983–7PubMedCrossRef
101.
Maloney AG, Schmucker DL, Vessey DA, et al. The effects of aging on the hepatic microsomal mixed function oxidase system of male and female monkeys. Hepatology 1986; 6: 282–7PubMedCrossRef
102.
Schmucker DL, Wang RK. Effects of aging on the properties of rhesus monkey liver microsomal NADPH cytochrome c (P-450) reductase. Drug Metab Dispos 1987; 15: 225–32PubMed
103.
Fujita S, Uesugi T, Kitagawa H, et al. Hepatic microsomal monooxygenase and A20 reductase activities in ageing Fischer 344 rats: importance of sex difference for ageing studies. In: Kitani K, editor. Liver and Aging -1982. Amsterdam: Elsevier Biomedical Press, 1982: 55–72
104.
Kamataki T, Maeda K, Shimada M, et al. 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. J Pharmacol Exp Ther 1985; 233: 222–8PubMed
105.
Schmucker DL, Vessey DA, Wang RK, et al. Does aging compromise hepatic microsomal monooxygenase activity? In: Bianchi L, Holt P, James OFW, et al., editors. Aging in liver and gastrointestinal tract. Falk Symposium 47. Lancaster: MTP Press, 1987: 241–254
106.
Tuenissen MW, Grivastava AK, Breimer OO. Influence of sex and oral contraceptives on antipyrine metabolite formation. Clin Pharmacol Ther 1987; 32: 240246
107.
Roberts RK, Desmond PV, Wilkinson GR, et al. Disposition of chlordiazepoxide: sex differences and effects of oral contraceptives. Clin Pharmacol Ther 1979; 25: 826–31PubMed
108.
Allen MD, Greenblatt DJ, Karmatz JS, et al. Desmethyl-diazepam kinetics in the elderly after oral prazepam. Clin Pharmacol Ther 1980; 28: 196–202PubMedCrossRef
109.
Greenblatt DJ, Allen MD, Harmatz JS, et al. Diazepam disposition determinants. Clin Pharmacol Ther 1980; 27: 301–12PubMedCrossRef
110.
Kremers P, Beaune P, Cresteil T, et al. Cytochrome P-450 monooxygenase activities in human and rat liver microsomes. Eur J Biochem 1981; 118: 599–606PubMedCrossRef
111.
James OFW, Rawlins MD, Woodhouse K. Lack of aging effect on human microsomal monooxygenase enzyme activities and on inactivation pathways for reactive metabolic intermediates. In: Kitani K, editor. Liver and Aging -1982. Amsterdam: Elsevier Biomedical Press, 1982: 395–408
112.
Woodhouse KW, Mutch E, Williams FM, et al. The effect of age on pathways of drug metabolism in human liver. Age Ageing 1984; 13: 328–34PubMedCrossRef
113.
Dumas C, Loi CM, Cusack BJ. Hepatic drug metabolism and aging. Clin Pharmacokinet 1990; 19: 359–89CrossRef
114.
Wynne HA, Mutch E, James OFW, et al. The effect of age upon the affinity of microsomal monooxygenase enzymes for substrate in human liver. Age Ageing 1988; 17: 401–5PubMedCrossRef
115.
Brodie MJ, Boobis AR, Bulpitt CJ, et al. Influence of liver disease and environmental factors on hepatic monooxygenase activity in vitro. Eur J Clin Pharmacol 1981; 20: 39–40PubMedCrossRef
116.
Arora S, Kassarjian Z, Krasinski SD, et al. Effect of age on tests of intestinal and hepatic function in healthy humans. Gastroenterology 1989; 96: 1560–5PubMed
117.
Schnegg M, Lauterburg BH. Quantitative liver function in the elderly assessed by galactose elimination capacity, aminopyrine demethylation and caffeine clearance. J Hepatol 1986; 3: 164–71PubMedCrossRef
118.
Zeeh J, Fuchs L, Bergmann W, et al. Influence of age, frailty and liver function on the pharmacokinetics of brofaromine. Eur J Clin Pharmacol 1996; 49: 387–91PubMedCrossRef
119.
Jorquera F, Almar M, Pozuelo M, et al. The effect of age and sex on metabolism and urinary excretion of antipyrine. J Gerontol A Biol Med Sci 1998; 53: M14–9CrossRef
120.
George J, Byth K, Farrell GC. Age but not gender selectively affects expression of individual cytochrome P450 proteins in human liver. Biochem Pharmacol 1995; 50: 727–30PubMedCrossRef
121.
Sotaniemi EA, Arranto AJ, Pelkonen O, et al. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 26 subjects with equal histopathologic conditions. Clin Pharmacol Ther 1997; 61: 331–9PubMedCrossRef
122.
Schmucker DL, Woodhouse KW, Wang RK, et al. Effects of age and gender on in vitro properties of human liver microsomal monooxygenases. Clin Pharmacol Ther 1990; 48: 365–74PubMedCrossRef
123.
Hunt CM, Westerkam WR, Stave GM, et al. Hepatic cytochrome P-4503A (CYP3A) activity in the elderly. Mech Ageing Dev 1992; 64: 189–99PubMedCrossRef
124.
Hunt CM, Westerkam WR, Stave GM. Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol 1992; 44: 275–83PubMedCrossRef
125.
Transon C, Lecoeur S, Leemann T, et al. Interindividual variability in catalytic activity and immunoreactivity of three major human liver cytochrome P450 isozymes. Eur J Clin Pharmacol 1996; 51: 79–85PubMedCrossRef
126.
Shimada T, Yamazaki H, Mimur M, et al. 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. J Pharmacol Exp Ther 1994; 270: 414–23PubMed
Metadata
Title
Liver Function and Phase I Drug Metabolism in the Elderly
A Paradox
Author
Douglas L. Schmucker
Publication date
01-11-2001
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 11/2001
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.2165/00002512-200118110-00005

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