David G. Le Couteur, MD, PhD, Professor of Geriatric Medicine, Centre for Education and Research on Ageing and ANZAC Research Institute, University of Sydney and Concord RG Hospital, Sydney, Australia.
Arthur Everitt, PhD, Associate Professor, Centre for Education and Research on Ageing, and Department of Physiology, University of Sydney, Sydney, Australia.
Michel Lebel, PhD, Associate Professor, Centre de Recherche en Cancérologie de l’Université Laval, Hôpital Hôtel-Dieu de Québec, Québec, PQ.

The liver undergoes substantial changes in structure and function in old age. There are age-related changes in liver mass, blood flow, and hepatocyte and sinusoidal cell morphology. These changes are associated with a significant impairment of many hepatic metabolic and detoxification activities, with implications for systemic aging and age-related disease. For example, the age-related impairment of the hepatic metabolism of lipoproteins predisposes to cardiovascular disease. The age-related decline in the hepatic clearance of most medications causes an increased risk of adverse drug reactions. Many of the beneficial effects of caloric restriction and caloric restriction mimetics such as resveratrol are mediated by their effects on the liver. Increasingly, the liver is seen as having a key role in aging.
Key words: liver, aging, hepatocyte, liver sinusoid, drug metabolism.

Dror Marchaim, MD, Department of Internal Medicine A, Asaf-Harofeh Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, IL.

Victor Dishy, MD, Department of Internal Medicine A, Asaf-Harofeh Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, IL.

Ahuva Golik, MD, Department of Internal Medicine A, Asaf-Harofeh Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, IL.

Geriatric clinical pharmacology is considered an established subdiscipline in the field of clinical pharmacology. This review will address some of the effects of aging on drug treatment in general, and will focus on specific classes of drugs commonly consumed by older adults: cardiovascular medications, non steroidal anti-inflammatory drugs, and psychoactive agents.

Key words: clinical pharmacology, older adults, drug metabolism, pharmacokinetics.

Lilia Malkin, BSc

Throughout the centuries, people have turned to medicinal substances to improve their health and quality of life. Today, medi-cations continue to be invaluable partners in humanity's war against disease. However, each person has a unique response to his or her medication(s). The differences among patients' reactions to pharmaceutical therapy can be at least partially explained by the inter-individual variation in drug metabolism. As biotechnology continues to make progress, the genetic foundation for illness and the consequent response to treatment is becoming increasingly apparent.^1,2 The basis for patient-to-patient variability in the effects of pharmaceutical agents has thus far been attributed predominantly to the drug-metabolizing capacity of the liver.¹ Accordingly, this article will focus on the hepatic biotransformation enzymes and the contribution of genetic polymorphism to individuals' thera-peutic responses and to treatment-related complications. It should be noted that tissue receptors and transporter proteins are also often subject to polymorphic variations, contributing to the variable response to medications and toxins; a discussion of this topic is, however, beyond the scope of this paper.

Hepatic Drug Metabolism Enzymes: An Overview
The metabolism and elimination of pharmaceutical agents may occur at several sites in the human body, including the liver, kidneys, gastrointestinal (GI) tract, lungs, and skin.