Pharmacokinetic considerations in obesity.

@article{Blouin1999PharmacokineticCI,
  title={Pharmacokinetic considerations in obesity.},
  author={Robert A. Blouin and Graham Warren},
  journal={Journal of pharmaceutical sciences},
  year={1999},
  volume={88 1},
  pages={
          1-7
        }
}
Obesity is a disease characterized as a condition resulting from the excess accumulation of body fat. In conjunction with increased stores of body fat, obesity has also been associated with increased mortality influenced by increased incidence of hypertension, atherosclerosis and coronary artery disease, diabetes, cancers of the breast, colon, prostate, endometrium, ovary, and cervix, and decreased overall survivability when compared with nonobese counterparts.1-5 As a consequence, obese… 

Effects of Obesity on Pharmacokinetics

  • G. Cheymol
  • Medicine, Biology
    Clinical pharmacokinetics
  • 2000
This review analyses recent publications on several classes of drugs: antibacterials, anticancer drugs, psychotropic drugs, anticonvulsants, general anaesthetics, opioid analgesics, neuromuscular blockers, β-blockers and drugs commonly used in the management of obesity.

Effects of obesity on drug pharmacokinetics

Obesity has been shown to play a central role in the metabolic syndrome, which increases the risk of developing cardiovascular disease 1.5to 3-fold and obese patients show a lower response to some antithrombotic agents which has suggested that dosage regimes should be adjusted for these subjects.

Drug disposition in obesity: toward evidence-based dosing.

Two methods to distinguish between developmental and obesity-related changes are proposed for obese children, and future research should focus on the characterization of physiological concepts to predict the optimal dose for each drug in the obese population.

The effects of obesity on drug pharmacokinetics in humans

This review presents material describing physiological changes that occur in the obese and their relationship to body composition, and various dosing metrics currently used to scale for size, and relationships between body composition and pharmacokinetic parameters.

Effect of Obesity on the Pharmacokinetics of Drugs in Humans

Clinicians should design treatment regimens that account for any significant differences in the CL and Vd in the obese, using a size descriptor that corrects for differences in absolute CL between obese and non-obese individuals.

Characterizing Pharmacokinetics in Children With Obesity—Physiological, Drug, Patient, and Methodological Considerations

Key considerations related to physiology, drug parameters, patient factors, and methodology that need to be accounted for while studying the influence of obesity on pharmacokinetics in children are highlighted and discussed.

Effects of obesity on liver cytochromes P450 in various animal models.

Results reported by various authors suggest that obesity is associated with a decrease of CYP activities, and the only exception is mouse obesity induced by monosodium glutamate (administered to newborn mice) as it usually leads to increased CYP expression.

Special Populations: Profiling the Effect of Obesity on Drug Disposition and Pharmacodynamics

  • K. Moore
  • Medicine, Biology
    Drug Discovery and Evaluation: Methods in Clinical Pharmacology
  • 2020
This chapter is a review of the available literature assessing the effects of obesity on the disposition and pharmacodynamics of some of the most commonly prescribed drugs and careful clinical decision making should always be used when applying literature from the population to individual patients and scenarios.

Pharmacokinetic Parameter Changes Observed in Obese Patients Changes Observed in Bariatric Surgery Patients

With an increasing prevalence of obesity, VTE, and ACS, more obese patients are being initiated on anticoagulant pharmacotherapy than ever before and this may be partly attributed to the development of a pro-inflammatory and prothrombotic state in obese patients.

Drug pharmacokinetics in the obese population: challenging common assumptions on predictors of obesity-related parameter changes

Clinical studies should focus on quantifying the impact of duration and severity of obesity on drug PK in adults and adolescents, and also include oral bioavailability and pharmacodynamics in these studies.
...

References

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  • Medicine, Biology
    Clinical pharmacokinetics
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Drug prescription for obese patients is difficult since dosages based on pharmacokinetic data obtained in normal-weight individuals could induce errors, and discrepancies in distribution in obesity exist between drugs belonging to different pharmacological classes.

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Physiologic changes associated with obesity and their effects on the distribution, protein binding, metabolism, and renal excretion of drugs are described. Changes in the volume of distribution

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The obese overfed rat appears to be superior to the obese Zucker rat as an animal model for evaluating the pharmacological consequences of human obesity, particularly those in which reproducing drug pharmacokinetics is an important consideration.

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In the obese, endogenous cortisol concentrations were initially higher before exogenous steroid dosing, were suppressed at an identical rate, and returned to baseline more slowly than in normal subjects, indicating that weight‐proportional dosage adjustments of this steroid in obesity should reflect TBW.

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Characterisation of appropriate animal models of obesity is underway to clarify the mechanisms for these in vivo pharmacokinetic observations in obese man, and further identification and understanding of the limitations of these models are forthcoming.

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Obesity occurring early in life affects intervening risk factors such as diabetes and hypertension much more strongly than that occurring later in life, when these risk factors become more important variables.

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Several equations, all based on the physico-chemical properties of a drug and the physiological changes in the obese subject, were used to compare the apparent volume of distribution, Vz as predicted by these equations with the Vz values of several drugs reported in the literature for obese subjects.

Effect of Obesity on Gentamicin Pharmacokinetics

Measuring serum concentrations and adjusting a patient's dosage regimen are imperative to ensure therapeutic serum concentrations, as a substantial interpatient variability existed in the measured distribution volume for all groups.

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  • Biology, Medicine
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Results showed obese rats to form more glucuronide and less sulfate conjugate than did pellet-fed controls, coinciding with clinical evidence for enhanced glucuronidation in obese humans.
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