Drug Metabolism and Pharmacokinetics in Malnutrition

Abstract

Malnutrition is usually complex. many deficiencies occurring simultaneously. Changes occur in almost every organ oj the body. Apart jrom the pathophysiological changes which occur in protein-calorie malnutrition. vitamin. mineral and trace element deficiency is accompanied by diverse metabolic changes in tissues. As a consequence there is large potentialjor alteration oj drug response in malnutrition. not only because of possible changes in drug kinetics but also because of changes in tissue uptake and localisation of drugs and potential alteration in drugreceptor interactions. The risk of susceptibility to drug-induced damage may also be increased.The functional status oj the gastroinlestinal tract is markedly altered in malnourished individuals and as a consequence the rate and extent of drug absorption is likely to be altered. First pass metabolism (intestinal and hepatic) is also likely to-be altered. The prqfi/eoj-plasma-proteins is considerably changed in malnourished individuals. In most cases. there is hypoalbuminaemia. the degree varying with the severity oj malnutrition. Globulins however. are elevated. particularly in cases oj injection. Lipoproteins are also reduced in states oj malnutri--'ion but there is no -it!formation ort ai-acid glycoproteins. which bind basic drugs. Malnutrition.by altering. the total body water. body composition and drug binding can lead to changes in the volume of distribution oj a drug. depending on its physicochemical properties and its ability to bind to macromolecules.Although electronmicroscopc studies indicate changes ill endoplasmic reticulum. liver junction in malnutrition seems to be generally well preserved. However. biotranllformation oj drugs may be altered due to changes in drug metabolising hepatic enzyme activity. alteration in drug binding characteristics qf proteins and the significant metabolic and hormonal changes in malnutrition. There may be abnormalities in biliary excretion which may affect drug elimination. at least in severe jorms of protein-calorie malnutrition. Severe malnutrition can lead to changes in cardiac and renal junction. These changes may be indirectly responsiblejor alterations in excretion mechanisms.Malnutrition can lead to changes in renal junction. although this may not be a uni/orm change and there are very little data on renal excretion mechanisms and their relationship to drug elimination in malnutrition. Cardiac function also seems to be affected in malnutrition. particularly in children. There is reduction in cardiac output and prolonged circulation time; changes which may indirectly be responsible for decreased renal and hepatic blood flow.Animal studies reveal that a number of macro-and micronutrient deficiencies can result in alteration in the rate qf drug metabolism. Deficiencies in proteins. dietary jat. minerals and vitamins have all been shown to influence the activity oj the mixed function oxidases. However. nutritional-pharmacological interactions in human populations are not as simple as observed

Age-Related Changes in the Gastrointestinal System

“…Moderate malnutrition has no effect. [66] The metabolism of drugs, such as paracetamol (acetaminophen), which are detoxified by glutathione S-transferase is influenced by prolonged fasting due to reduction of the glutathione pool. Increased toxicity of paracetamol is well known in alcoholics where the glutathione stores in the liver have been demonstrated to be reduced.l 67 ,68] Caloric and protein excess was able to increase the clearance of phenazone (antipyrine) and aminophenazone (aminopyrine), but the changes were rarely of clinical importance.l 69 ]…”

Drug–Nutrient Interactions: A Broad View with Implications for Practice

“…Pharmacokinetic and pharmacodynamic data are much less frequently assessed based on nutrition status (eg, protein-calorie malnutrition, obesity, micronutrient deficits), although the influence on drug metabolism has been recognized previously (6,(65)(66)(67). Drug distribution and drug clearance are the two parameters most likely to be influenced by malnutrition, with the potential-if not recognized and addressed by modifying the initial dose or maintenance dose, respectively-to alter clinical response (68,69).…”

“…This began to shift with isolated reports-now considered classic findings-such as the influence of vitamin C deficiency on barbiturate action (3), the influence of isoniazid on vitamin B-6 metabolism (4), and the influence of iron on tetracycline absorption (5). There were also classic reviews on the impact of malnutrition on drug metabolism (6), the effect of food on drug absorption (7), and the influence of drugs on nutrient disposition (8). By then, the most clinically recognized DNIs were the result of intraluminal interactions between drugs (eg, levodopa, tetracycline) and food (7).…”

Protein malnourishment: A predisposing factor in acrylamide toxicity in pregnant rats

“…Various factors such as disease condition, age, sex, diet, and environmental chemicals have been reported to predispose individuals to drugs and chemicals (Krishnaswamy, 1983;Mendenhall et al, 1986). Humans living in developing countries have generally been found to suffer from various physiological and functional disorders due to vitamin and mineral deficiencies, undernutrition, and protein energy malnutrition (Chopra et al, 1986).…”

“…The rates of absorption, distribution, and elimination of drugs are altered by nutritional factors (Krishnaswamy, 1983;Krishnaswamy and Naidu, 1977;Narang et al, 1977). A reduction in the brain glutathione levels suggests poor detoxication process in these rats.…”