Drug disposition in obesity and protein–energy malnutrition

Abstract

Clinical response to medication can differ between patients. Among the known sources of variability is an individual's nutrition status. This review defines some pharmacokinetic terms, provides relevant body size metrics and describes the physiologic influences of protein-energy malnutrition and obesity on drug disposition. Weight-based drug dosing, which presumes a healthy BMI, can be problematic in the protein-energy malnourished or obese patient. The use of total body weight, lean body weight, or an adjusted body weight depends on the drug and how it is differently handled in malnutrition or obesity. Most of the recognized influences are seen in drug distribution and drug elimination as a result of altered body composition and function. Distribution characteristics of each drug are determined by several drug-related factors (e.g. tissue affinity) in combination with body-related factors (e.g. composition). Drug elimination occurs through metabolic and excretory pathways that can also vary with body composition. The current data are limited to select drugs that have been reported in small studies or case reports. In the meantime, a rational approach to evaluate the potential influences of malnutrition and obesity can be used clinically based on available information. Antimicrobials are discussed as a useful example of this approach. Further advancement in this field would require collaboration between experts in body composition and those in drug disposition. Until more data are available, routine monitoring by the clinician of the protein-energy malnourished or obese patient receiving weight-based drug regimens is necessary.Drug: Obesity: Protein-energy malnutrition: Pharmacokinetics: Drug-nutrient interactionThe clinical variability that exists among patients is wellrecognized by most clinicians. This inter-individual variability includes the response to a drug which can be accounted for by a number of factors. Appropriate patient care requires an appreciation of the factors that influence the disposition and effect of medication. As used here, the term disposition refers to the absorption, distribution and elimination of a drug; while the term effect reflects the physiologic action of the drug at the target tissue or cell. The sources of variability that influence medication are numerous and include age, life stage, sex, genotype, disease state and nutrition status (1) . The latter is the focus of this review and encompasses primary protein-energy malnutrition (PCM) and obesity.The influence that nutrition status can have on drug disposition and effect is included as one of the five broad categories in the classification of drug-nutrient interactions (2,3)

Impact of pretransplant body mass index on the clinical outcome after allogeneic hematopoietic SCT

“…In addition, several previous reports showed that the status of nutrition had an impact on the metabolism of the chemotherapeutic drugs. 29,30 For instance, nutritional status was reported to affect the level of cytochrome P450 enzymes which are responsible for the metabolism of the chemotherapeutic drugs. It was reported that there was a correlation between total body weight and plasma half-life of CY, which means that the concentration of CY is higher in obese patients compared with the normal weight patients.…”

Drug and nutrition interactions: not just food for thought

“…31,32 Weight-based drug dosing regimens are not reflective of drug disposition in malnourished and obese patients. 31,33 This is further complicated when relying on body surface area or 'ideal' body weight rather than on more appropriate metrics for dosing medication. 31,34 The precipitating factor of an interaction may also be the drug itself.…”

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).…”

“…One unfortunate aspect of weight-based dosing in practice is the use of empiric "ideal" body weight equations (75,76), or the incorporation of these tenuous values into an "adjusted" body weight equation. In the latter equation, the correction factor used is rarely drug-specific (69). An evidence-based estimate of lean body weight is suggested as a more appropriate metric in determining dosing weight for obese patients (69,77,78).…”

“…In the latter equation, the correction factor used is rarely drug-specific (69). An evidence-based estimate of lean body weight is suggested as a more appropriate metric in determining dosing weight for obese patients (69,77,78). The direction and magnitude of change in volume of distribution or clearance of a drug is unique to the drug and cannot be generalized across all drugs based simply on the presence of obesity or protein-calorie malnutrition.…”