Canadian Journal of Cardiology

The Impact of Obesity on the Pharmacology of Medications Used for Cardiovascular Risk Factor Control

Published:October 27, 2014DOI:


      Most drugs are currently dosed empirically (fixed-dose) or based on total body weight. In obese patients, these dosing strategies might, in theory, lead to inadequate clinical effect (empiric dosing) or toxicity (weight-based dosing). Our objective was to first review body size descriptors used for drug dosing and then to examine the effect of obesity on the pharmacokinetics and pharmacodynamics of drugs used for cardiovascular risk reduction (antihypertensive agents, statins, aspirin, antidiabetic agents). We found a limited number of published studies for most drug classes. For β-blockers, volume of distribution was increased in the obese and this appears to be primarily due to greater distribution into lean tissue. In contrast, clearance was decreased, unchanged or increased, depending on the agent. This suggests that loading doses should be based on lean body weight and maintenance doses adjusted in a drug-specific fashion according to clearance alterations. For antidiabetic agents, glucose-lowering effects were slightly diminished in most studies in obese patients. Outside of these findings, in the studies reported to date, obesity did not exert a consistent, clinically important effect on drug pharmacology. Because obesity can cause drug-specific pharmacological changes for some drug classes (eg, β-blockers), there is a need to conduct further studies. To avoid detecting pharmacokinetic changes that are ultimately deemed clinically inconsequential, we suggest a “top down” approach in which clinically important outcomes are compared between obese and nonobese subjects. If important differences are found, further studies should be then performed to delineate underlying pharmacological mechanisms and inform the need for dose adjustment.


      La plupart des médicaments sont habituellement dosés de manière empirique (doses fixes) ou selon le poids corporel total. Chez les patients obèses, ces stratégies de dosage entraîneraient, en théorie, un effet clinique inadéquat (dosage empirique) ou une toxicité (dosage établi selon le poids). Notre objectif était d’abord de passer en revue les descripteurs de la masse corporelle utilisés pour doser les médicaments et ensuite d’examiner l’effet de l’obésité sur la pharmacocinétique et la pharmacodynamie des médicaments utilisés pour réduire le risque cardiovasculaire (antihypertenseurs, statines, aspirine, antidiabétiques). Nous avons trouvé un nombre limité d’études publiées sur la plupart des classes de médicaments. En ce qui concerne les β-bloquants, le volume de distribution était augmenté chez l’obèse, ce qui semble être principalement dû à la plus grande distribution dans les tissus maigres. En revanche, la clairance était diminuée, inchangée ou augmentée selon l’agent. Cela suggère que les doses de charge devraient être établies selon la masse du corps excluant la graisse et les doses d’entretien ajustées de manière spécifique au médicament selon les modifications de la clairance. En ce qui concerne les antidiabétiques, les effets hypoglycémiants étaient légèrement diminués dans la plupart des études chez les patients obèses. Au-delà de ces résultats, les études rapportées à ce jour ont démontré que l’obésité n’exerçait pas de manière constante un effet cliniquement important sur la pharmacologie. Puisque l’obésité peut causer des changements pharmacologiques spécifiques au médicament pour certaines classes de médicaments (p. ex., les β-bloquants), il est nécessaire de mener d’autres études. Pour éviter la détection de changements pharmacocinétiques, qui sont finalement considérés cliniquement sans conséquence, nous suggérons une approche « descendante » où les résultats importants sur le plan clinique sont comparés entre les sujets obèses et les sujets non obèses. Si des différences importantes sont observées, d’autres d’études devraient alors être réalisées pour définir les mécanismes pharmacologiques sous-jacents et appuyer la nécessité de l’ajustement des doses.
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