Skip to main content
SpringerLink
Log in

Drug Hepatotoxicity in the Elderly

  • Chapter
Drug-Induced Hepatotoxicity

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 121))

Abstract

Hepatotoxicity of drugs is a consequence of many different processes occurring in the liver, including the sensitivity of the liver to drugs and the metabolism in the liver for the detoxification and activation of drugs (MITCHELL and JOLLOWS 1975), all of which may be affected by aging. Despite an earlier suggestion by clinicians that the elderly may be more susceptible to drug hepatotoxicity, there has been no conclusive data to confirm this hypothesis. In this chapter, past clinical information on this topic will be briefly reviewed first. This will be followed by a summary of past experimental studies on animals, in particular rodents in comparison to humans. Unfortunately, the results from experimental animals are often difficult to extrapolate to clinical situations for various reasons. However, a comprehensive but critical review of the past data in experimental animals may be of help for the proper interpretation of these data and for the future elucidation of this complicated but very important clinical and experimental problem.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abernathy CO, Lukacs L, Zimmerman HJ (1980) Cytotoxic effects of erythromycin estolate and chlorpromazine on hepatocytes isolated from rats of varying ages: a brief note. Mech Ageing Dev 12:1–6

    Article  PubMed  CAS  Google Scholar 

  • Baillie SP, Yelland C, Woodhouse KW (1989a) Hepatic adverse drug reactions in the elderly. Adverse Drug React Acute Po is Rev 8:153–163

    CAS  Google Scholar 

  • Baillie SP, Bateman DN, Coates PE, Woodhouse KW (1989b) Age and the pharmacokinetics of morphine. Age Ageing 18:258–262

    Article  PubMed  CAS  Google Scholar 

  • Boobis AR, Davies DS (1984) Human cytochrome P-450. Xenobiotica 14:151–185

    Article  PubMed  CAS  Google Scholar 

  • Cand F, Verdetti W (1989) Superoxide dismutase, glutathione peroxidase, catalase, and lipid peroxidase, in major organs of the aging rats. Free Rad BioI Med 7:59– 63

    Article  CAS  Google Scholar 

  • Cao-Danh H, Benedetti MS, Dostert P (1983) Differential changes in superoxide dismutase activity in brain and liver of old rats and mice. J Neurochem 40:1003– 1007

    Article  Google Scholar 

  • Carrillo ME, Kitani K, Kanai S, Sato Y, Nokubo M, Ohta M, Otsubo K (1989) Differences in the influence of diet on hepatic glutathione S-transferase activity and glutathione content between young and old C57 black female mice. Mech Ageing Dev 47:1–15

    Article  PubMed  CAS  Google Scholar 

  • Carrillo MC, Nokubo M, Sato Y, Kanai S, Ohta M, Kitani K (1990) Effect of proteinfree diet on activities and subunits of glutathione S-transferase in livers of young and aged female rats. Mech Ageing Dev 56:237–251

    Article  PubMed  CAS  Google Scholar 

  • Carrillo MC, Nokubo M, Kitani K, Satoh K, Sato K (1991) Age-related alterations of enzyme activities and subunits of hepatic glutathione S-transferases in male and female Fischer-344 rats. Biochim Biophys Acta 1077:325–331

    Article  PubMed  CAS  Google Scholar 

  • Carrillo MC, Kanai S, Sato Y, Kitani K (1992) Age-related changes in antioxidant enzyme activities are region and organ selective as well as sex in the rat. Mech Ageing Dev 65:187–198

    Article  PubMed  CAS  Google Scholar 

  • Chengelis CP (1988) Age- and sex-related changes in epoxide hydrolase, UDP- glucuronosyl transferase, glutathione S-transferase, and PAPS sulphotransferase in Sprague-Dawley rats. Xenobiotica 18:1225–1237

    Article  PubMed  CAS  Google Scholar 

  • Coecke S, Vandenberghe Y, Callaerts A, Sonck W, Verleye G, VanBezooijen CFA, Vercruysse A, Rogiers V (1990) Hepatic cytosolic glutathione S-transferase activities in ageing Brown Norway rats - importance of sex differences and phenobarbital treatment for studies of ageing. Mech Ageing Dev 55:189–198

    Article  PubMed  CAS  Google Scholar 

  • Denison H, Kaczynski J, Wallerstedt S (1987) Paracetamol medication and alcohol abuse: a dangerous combination for the liver and the kidney. Scand J Gastroenterol 22:701–704

    Article  PubMed  CAS  Google Scholar 

  • Erickson CK (1984) Ethanol clearance in nine inbred rat strains. Alcohol Clin Exp Res 8:491–494

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Checa JC, Ookhtens M, Kaplowitz N (1989) Effects of chronic ethanol feeding on rat hepatocytic glutathione. Relationship of cytosolic glutathione to efflux and mitochondrial sequestration. J Clin Invest 83:1247–1252

    Article  PubMed  CAS  Google Scholar 

  • Fujita S, Kitagawa H, Chiba M, Suzuki T, Ohta M, Kitani K (1985a) Age and sex associated differences in the relative abundance of multiple species of cytochrome P-450 in rat liver microsomes - a separation by HPLC of hepatic microsomal cytochrome P-450 species. Biochem Pharmacol 34:1861–1864

    Article  PubMed  CAS  Google Scholar 

  • Fujita S, Kitagawa H, Ishizawa H, Suzuki T, Kitani K (1985b) Age associated alterations in hepatic glutathione-S-transferase activities. Biochem Pharmacol 34:3891–3894

    Article  PubMed  CAS  Google Scholar 

  • Fujita S, Chiba M, Suzuki T, Kitani K (1986)Effect of senescence on the hepatic metabolism of drgus affecting the central nervous system in rats and mice. In: Kitani K (ed) Liver and aging - 1986, liver and brain. Elsevier Science. Amsterdam, pp 103–112

    Google Scholar 

  • Galinsky RE, Corcoran GB (1986) Influence of advanced age on the formation and elimination of acetaminophen metabolites by male rats. Pharmacology 32:312–320

    Article  Google Scholar 

  • Galinsky RE, Kane RE, Franklin MK (1986) Effect of aging on drug metabolizing enzymes important in acetaminophen elimination. J Pharmacol Exp Ther 237: 107– 113

    Google Scholar 

  • Galinsky RE, Johnson DH, Kane RE, Franklin MR (1990) Effect of aging on hepatic biotransformation in female Fischer 344 rats: changes in sulfotransferase activities are consistent with known gender related changes in pituitary growth hormone secretion in aging animals. J Pharmacol Exp Ther 255:577–583

    PubMed  CAS  Google Scholar 

  • Gellert J, Geisbüsch B, Teschke R (1988)Impaired ethanol metabolism with advancing age in female rats: studies on its mechanism. Adv Biosci 71:225–229

    CAS  Google Scholar 

  • Goudie BM, Birnie GF, Watkinson Get al. (1982) Jaundice associated with the use of benoxaprofen. Lancet 1:959–961

    Article  PubMed  CAS  Google Scholar 

  • Herd B, Wynne H, Wright P, Lames O, Woodhouse K (1991) The effect of age on glucuronidation and sulphation of paracetamol by human liver fractions. Br J Clin Pharmacol 32:768–770

    PubMed  CAS  Google Scholar 

  • Hornbrook KR, Kosanke SD, Rikans LE (1993) Aged mice are resistant to the hepatotoxic effects of endotoxin and galactosamine. Exp Mol Pathol 59:27–37

    Article  PubMed  CAS  Google Scholar 

  • James OFW (1988) Parenchymal liver disease in the elderly. In: Bianchi L, Holt P, James OFW (eds) Aging in liver and gastrointestinal tract. MTP Press. Lancaster, pp 359–369

    Google Scholar 

  • James OFW. Rawlins MD, Woodhouse K (1982)Lack of ageing effect on human microsomal monooxygenase enzyme activities and on inactivation pathways for reactive metabolic intermediates. In: Kitani K (ed) Liver and aging-1982. Elsevier Biomedical, Amsterdam, pp 395–408

    Google Scholar 

  • Ji LL. Dillon D. Wu E (1990) Alteration of antioxidant enzymes with aging in rat skeletal muscle and liver. Am J Physiol 27:R918–923

    Google Scholar 

  • Kamataki T, Maeda K, Shimada M, Kitani K, Nagai T, Kato R (1985) Age-related alteration 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 233:222–228

    PubMed  CAS  Google Scholar 

  • Kato R, Takanaka A (1968)Metabolism of drugs in old rats. I. Activities of NADPH linked electron transport and drug-metabo-lizing enzyme systems in liver microsomes of old rats. Jpn J PharmacoI 18:381–388

    Article  CAS  Google Scholar 

  • Kato R, Vassanelli P, Frontino G, Chiesara E (1964) Variation in the activity of liver microsomal drug metabolizing enzymes in rats in relation to the age. Biochem Pharmacol 13:1037–1051

    Article  PubMed  CAS  Google Scholar 

  • Kellogg EW, Fridovich J (1976) Superoxide dismutase in the rat and mouse as a function of age and longevity. J Gerontol 31:405–408

    PubMed  CAS  Google Scholar 

  • Kitahara A, Ebina T, Ishikawa T, Soma Y, Sato K, Kanai S (1982) Changes in activities and molecular forms of rat hepatic drug metabolizing enzymes during aging. In: Kitani K (ed) Liver and aging-1982, liver and drugs. Elsevier Biomedical, Amsterdam, pp 135–143

    Google Scholar 

  • Kitani K (1986) Does the liver age in man? (Editorial) Hepatol Rapid Rev 16:V–XIX

    Google Scholar 

  • Kitani K (1988) Drugs and the ageing liver. Life Chern Rep 6:143–230

    CAS  Google Scholar 

  • Kitani K (1990a) Evaluation of rodent models for the study of age-related modifications in toxic response. In: Volans GN, Sims J, Sullivan FM, Turner P (eds) Basic science in toxicology. Proceedings of the 5th international congress on toxicology. Taylor and Francis, London, pp 422–431

    Google Scholar 

  • Kitani K (1990b) Aging and the liver. In: Popper H, Schaffner F (eds) Progress in liver diseases, vol IX. Saunders, Philadelphia, pp 603–623

    Google Scholar 

  • Lammi-Keefe CJ, Swan PB, Hegarty PVJ (1984) Copper-zinc and manganese superoxide dismutase activity in brain and liver of old rats and mice. J Neurochem 40:1003–1 007

    Google Scholar 

  • Lauterburg BH, Velez ME (1988) Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity. Gut 29:1153–1157

    Article  PubMed  CAS  Google Scholar 

  • Lauterburg BH, Vaishnav Y, Stillwell WG, Mitchell JR (1980) The effects of age and glutathione depletion on hepatic glutathione turnover in vivo determined by acetaminophen probe analysis. J Pharmacol Exp Ther 213:54–58

    PubMed  CAS  Google Scholar 

  • Leakey JA, Cunny HC, Bazare J Jr, Webb PJ, Lipscomb JC, Slikker W Jr, Feuers RJ, Duffy PH, Hart RW (1989) Effects of aging and caloric restriction on hepatic drug metabolizing enzymes in the Fischer 344 rats. II: effects on conjugating enzymes. Mech Ageing Dev 48:157–166

    CAS  Google Scholar 

  • Lee DW, Yu BP (1991) The age-related alterations in liver microsomal membranes: the effect of lipid peroxidation and dietary restriction. In: Kitani K (ed) Liver and aging―1990. Excerpta Medica, Amsterdam, pp 17–29

    Google Scholar 

  • Maloney AG, Schmucker DL, Vessey DS, Wang RK (1986) The effects of aging on the hepatic microsomal mixed function oxidase system of male and female monkeys. Hepatology 6:282–287

    Article  PubMed  CAS  Google Scholar 

  • Mannervik B, Alin P, Guthenberg C, Jensson H, Tahir MK, Warholm M, Jörnvall H (1985)Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Nat! Acad Sci USA 82:7202–7206

    Article  PubMed  CAS  Google Scholar 

  • Mitchell JR, Jollows DJ (1975) Metabolic activation of drugs to toxic substances. Gastroenterology 68:392–410

    PubMed  CAS  Google Scholar 

  • Mitchell JR, Jollow J, Potter WZ, Gillette JR, Brodie BB (1973) Acetaminopheninduced hepatic necrosis. IV. Protective role of glutathione. J Pharmacol Exp Ther 187:211–217

    CAS  Google Scholar 

  • Mitchell JR, Thorgeirsson SS, Potter WZ, Jollow DJ, Keiser H (1974) Acetaminopheninduced hepatic injury: protective role of glutathione in man and rationale for therapy. Clin Pharmacol Ther 16:676–684

    PubMed  CAS  Google Scholar 

  • Neuberger J, Williams R (1984) Halothane anaesthesia and liver damage. Br Med J 289:1136–1139

    Article  CAS  Google Scholar 

  • Oliver CN, Levine RL, Stadtman ER (1987) A role of mixed function oxidation reactions in the accumulation of altered enzyme forms during aging. J Geriatr Soc 947–956

    Google Scholar 

  • Ott JF, Hunter BE, Walker DW (1985) The effect of age on ethanol metabolism and on the hypothermic and hypnotic responses to ethanol in the Fischer 344 rat. Alcohol Clin Exp Res 9:59–65

    Article  PubMed  CAS  Google Scholar 

  • Rao G, Xia E, Richardson A (1990) Effect of age on the expression of antioxidant enzymes in male Fischer F-344 rats. Mech Ageing Dev 53:49–60

    Article  PubMed  CAS  Google Scholar 

  • Reiss U, Gershon D (1976) Comparison of cytoplasmic superoxide dismutase in liver, heart and brain of aging rats and mice. Biochem Biophys Res Commun 73:255–261

    Article  PubMed  CAS  Google Scholar 

  • Reiss U, Gershon D (1978) Methionine sulfoxide reductase: a novel protective enzyme in liver and its potentially significant role in aging. In: Kitani K (ed) Liver and aging -1978. Elsevier/North-Holland Biomedical, Amsterdam, pp 55–61

    Google Scholar 

  • Rikans LE (1984) Influence of aging on the susceptibility of rats to hepatotoxic injury. Toxicol Appl Pharmacol 73:243–249

    Article  PubMed  CAS  Google Scholar 

  • Rikans LE (1987) The oxidation of acrolein by rat liver aldehyde dehydrogenases. Relation to allyl alcohol hepatotoxicity. Drug Metab Dispos 15:356–362

    CAS  Google Scholar 

  • Rikans LE (1989) Influence of aging on chemically induced hepatotoxicity: role of agerelated changes in metabolism. Drug Metab Rev 20:87–110

    Article  PubMed  CAS  Google Scholar 

  • Rikans LE, Cai Y (1992) Age-associated enhancement of diquat-induced lipid peroxidation and cytotoxicity in isolated rat hepatQcytes. J Pharmacol Exp Ther 262:271–278

    PubMed  CAS  Google Scholar 

  • Rikans LE, Cai Y (1993) Diquat-induced oxidative damage in BCNU-pretreated hepatocytes of mature and old rats. Toxicol Appl Pharmacol 118:263–270

    Article  PubMed  CAS  Google Scholar 

  • Rikans LE, Kling R (1987) Effects of aging and testosterone administration on liver alcohol dehydrogenase activity in male Fischer 344 rats. Alcohol Clin Exp Res 11 :562–566

    Article  PubMed  CAS  Google Scholar 

  • Rikans LE, Kosanke SD (1984) Effect of aging on liver glutathione levels and hepatocellular injury from carbon tetrachloride, allyl alcohol or galactosamine. Drug Chern Toxicol 7:595–604

    Article  CAS  Google Scholar 

  • Rikans LE, Moore DR (1987) Effect of age and sex on allyl alcohol hepatotoxicity in rats: role of liver alcohol and aldehyde dehydrogenase activities. J Pharmacol Exp Ther 243:20–26

    PubMed  CAS  Google Scholar 

  • Rikans LE, Moore DR (1988) Acetaminophen hepatotoxicity in aging rats. Drug Chern Toxicol 11:237–247

    Article  CAS  Google Scholar 

  • Rikans LE, Snowden CD (1989) Effects of acute ethanol administration on female rat liver as a function of aging. Life Sci 45:1373–1379

    Article  PubMed  CAS  Google Scholar 

  • Rikans LE, Moore DR, Snowden CD (1991) Sex-dependent differences in the effects of aging on antioxidant defense mechanisms of rat liver. Biochim Biophys Acta 1074:195–200

    PubMed  CAS  Google Scholar 

  • Rikans LE, Kitani K, Nokubo M, Kanai S (1992a) Hepatic glutathione (GSH) regulation in young and old C57BL mice. Toxicologist 12:418 (abstract)

    Google Scholar 

  • Rikans LE, Nokubo M, Kanai S, Kitani K (1992b) Diurnal variation in hepatic glutathione content as a function of age. Drug Dev Res 26:461–465

    Article  CAS  Google Scholar 

  • Rikans LE, Snowden CD, Moore D (1992c) Effect of aging on enzymatic antioxidant defenses in rat liver mitochondria. Gerontology 38:133–138

    Article  PubMed  CAS  Google Scholar 

  • Rogen GM, Singletary WV Jr, Rauckman EJ, Killenberg PG (1983) Acetaminophen hepatotoxicity. An altern(ltive mechanism. Riochcm Pharmacol 32:2053–2059

    Google Scholar 

  • Rogiers V, Coecke S, Vandenberghe Y, Morel F, Callaerts A, Verleye G, VanBezooijen CFA, Guillouzo A, Vercruysse A (1991) Effect of the aging process on the gender and phenobarbital dependent expression of glutathione S-transferase subunits in Brown Norway rat liver. Biochem Pharmacol 42:491–498

    Article  PubMed  CAS  Google Scholar 

  • Rubin E, Lieber CS (1972) Ethanol metabolism in the liver. In: Popper H, Schaffner F (eds) Progress in liver diseases, vol IV. Grune and Stratton, New York, pp 549– 566

    Google Scholar 

  • Seitz HK, Meydani M, Ferschke I, Simanowski UA, Boesche J, Bogusz M, Hoepker W, Blumberg JB, Russell RM (1989) Effect of aging on in vivo and in vitro ethanol metabolism and its toxicity in F344 rats. Gastroenterology 97:446–456

    PubMed  CAS  Google Scholar 

  • Semsei I, Rao G, Richardson A (1989) Changes in the expression of superoxide dismutase and catalase as a function of age and dietary restriction. Biochem Biophys Res Commun 164:620–625

    Article  PubMed  CAS  Google Scholar 

  • Spearman ME, Leibman KC (1983) Hepatic and pulmonary cytosolic metabolism of epoxides effects of aging on conjugation with glutathione. Life Sci 33:2615–2625

    Article  PubMed  CAS  Google Scholar 

  • Spearman ME, Leibman KC (1984a) The effects of aging on hepatic and pulmonary glutathione S-transferase activities in male and female Fischer 344 rats. Biochem Pharmacol 33:1309–1313

    Article  PubMed  CAS  Google Scholar 

  • Spearman ME, Leibman KC (1984b) Aging selectively alters glutathione S-transferase isozyme concentrations in liver and lung cytosol. Drug Metab Dispos 12:661–671

    PubMed  CAS  Google Scholar 

  • Stohs SJ, AI-Turk WA, Angle CR (1982) Glutathione S-transferase and glutathione reductase activities in hepatic and extrahepatic tissues of female mice as a function of age. Biochem Pharmacol 31:2113–2116

    Article  PubMed  CAS  Google Scholar 

  • Sutter MA, Gibson G Williams LS, Wang RK, Schmucker DL (1985) Comparison of the hepatic mixed function oxidase systems of young, adult and old non-human primates (Macaca nemestrina). Biochem Pharmacol 34:2983–2987

    Article  PubMed  CAS  Google Scholar 

  • Sweeny DJ, Weiner M (1985) Metabolism of acetaminophen in hepatocytes isolated from mice and rats of various ages. Drug Metab Dispos 13:377–379

    PubMed  CAS  Google Scholar 

  • Taggart HM, Alderdyce JM (1982) Fatal cholestatic jaundice in elderly patients taking benoxaprofen. Br Med J 284:1372

    Article  CAS  Google Scholar 

  • Tarloff JB, Goldstein RS, Sozio RS, Hook JB (1991) Hepatic and renal conjugation (phase II) enzyme activities in young adult, middle-aged, and senescent male Sprague-Dawley rats. Proc Soc Exp Biol Med 197:297–303

    PubMed  CAS  Google Scholar 

  • Vestal RE, McGuire EA, Tobin JD, Andres R, Norris AH, Mezey E (1977) Aging and ethanol metabolism. Clin Pharmacol Ther 21:343–354

    PubMed  CAS  Google Scholar 

  • Wiberg GS, Trenholm HL, Coldwell BB (1970) Increased ethanol toxicity in old rats: changes in LD50, in vivo and in vitro metabolism, and liver alcohol dehydrogenase activity. Toxicol Appl Pharmacol 16:718–727

    Article  PubMed  CAS  Google Scholar 

  • Woodhouse K, Herd B (1993) The effect of age and gender on glucuronidation and sulphation in rat liver: a study using paracetamol as a model substrate. Arch Gerontol Geriatr 16:111–115

    Article  PubMed  CAS  Google Scholar 

  • Woodhouse KW,Mortimer O,Wiholm BE (1986) Hepatic adverse drug reactions: the influence of age. In: Kitani K (ed) Liver and aging―1986, liver and brain. Elsevier Science, Amsterdam, pp 75–80

    Google Scholar 

  • Wulf JH, Cutler RG (1979) Altered protein hypothesis of mammalian aging process I, thermal stability of glucose-6-phosphate dehydrogenase in C57BL/6J mouse tissues. Exp Gerontol 9:189–196

    Google Scholar 

  • Wynne HA, Mutch E, James OFW, Rawlins MD, Woodhouse KW (1987) The effect of age on mono-oxygenase enzyme kinetics in rat liver microsomes. Age Ageing 16:153–158

    Article  PubMed  CAS  Google Scholar 

  • Wynne HA, Mutch E, James OFW, Wright P, Rawlins MD, Woodhouse KW (1988) The effect of age upon the affinity of microsomal mono-oxygenase enzymes for substrate in human liver. Age Ageing 17:401–405

    Article  PubMed  CAS  Google Scholar 

  • Wynne HA, Cope LH, Herd B, Rawlins MD, James OFW, Woodhouse KW (1990) The association of age and frailty with paracetamol conjugation in man. Age Ageing 19:419–424

    Article  PubMed  CAS  Google Scholar 

  • Zs.-Nagy I, Kitani K, Ohta M, Imahori K (1986) Age-dependent decrease of the lateral diffusion constant of proteins in the plasma membrane of hepatocytes as revealed by fluorescence recovery after photobleaching in tissue smears. Arch Gerontol Geriatr 5:131–146

    Article  PubMed  CAS  Google Scholar 

  • Zs.-Nagy I, Kitani K, Ohta M (1989) Age-dependence of the lateral mobility of proteins in the plasma membrane of hepatocytes of C57/BL/6 mice: FRAP studies on liver smears. J Gerontol Bioi Sci 44:B83–B87

    CAS  Google Scholar 

Download references

Authors
  1. K. Kitani
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pathology Division of Experimental Pathology, University of Toronto, Medical Sciences Building, 1 King’s College Circle, M5S 1A8, Toronto, Ontario, Canada

    Ross G. Cameron M.D., Ph.D.

  2. Department of Clinical Biochemistry Banting Institute, University of Toronto, Room 521, 100 College Street, M5G 1L5, Toronto, Ontario, Canada

    George Feuer Ph.D.

  3. Parke-Davis Pharmaceutical Research Division Department of Pathology and Experimental Toxicology, Warner Lambert Company, 2800 Plymouth Road, 48105, Ann Arbor, MI, USA

    Felix A. de la Iglesia M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Kitani, K. (1996). Drug Hepatotoxicity in the Elderly. In: Cameron, R.G., Feuer, G., de la Iglesia, F.A. (eds) Drug-Induced Hepatotoxicity. Handbook of Experimental Pharmacology, vol 121. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61013-4_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-61013-4_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64657-7

  • Online ISBN: 978-3-642-61013-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation