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Drug Disposition in Obesity: Toward Evidence-Based Dosing

Obesity and morbid obesity are associated with many physiological changes affecting pharmacokinetics, such as increased blood volume, cardiac output, splanchnic blood flow, and hepatic blood flow. In obesity, drug absorption appears unaltered, although recent evidence suggests that this conclusion m... Full description

Journal Title: Annual review of pharmacology and toxicology 2015-01-06, Vol.55 (1), p.149-167
Main Author: Knibbe, Catherijne A.J
Other Authors: Brill, Margreke J.E , van Rongen, Anne , Diepstraten, Jeroen , van der Graaf, Piet Hein , Danhof, Meindert
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Annual Reviews
ID: ISSN: 0362-1642
Link: https://www.ncbi.nlm.nih.gov/pubmed/25340929
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recordid: cdi_pubmed_primary_25340929
title: Drug Disposition in Obesity: Toward Evidence-Based Dosing
format: Article
creator:
  • Knibbe, Catherijne A.J
  • Brill, Margreke J.E
  • van Rongen, Anne
  • Diepstraten, Jeroen
  • van der Graaf, Piet Hein
  • Danhof, Meindert
subjects:
  • Administration, Oral
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Animals
  • Biological Availability
  • Body Mass Index
  • Body Weight
  • Child
  • childhood
  • children
  • Drug Dosage Calculations
  • Evidence-Based Medicine - methods
  • Female
  • Gastrointestinal Absorption
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • morbidly obese
  • obese
  • Obesity - diagnosis
  • Obesity - metabolism
  • Obesity - physiopathology
  • Pharmaceutical Preparations - administration & dosage
  • Pharmaceutical Preparations - metabolism
  • pharmacodynamics
  • Pharmacokinetics
  • precision medicine
  • prediction in pharmacology
  • Tissue Distribution
  • Young Adult
ispartof: Annual review of pharmacology and toxicology, 2015-01-06, Vol.55 (1), p.149-167
description: Obesity and morbid obesity are associated with many physiological changes affecting pharmacokinetics, such as increased blood volume, cardiac output, splanchnic blood flow, and hepatic blood flow. In obesity, drug absorption appears unaltered, although recent evidence suggests that this conclusion may be premature. Volume of distribution may vary largely, but the magnitude and direction of changes seem difficult to predict, with extrapolation on the basis of total body weight being the best approach to date. Changes in clearance may be smaller than in distribution, whereas there is growing evidence that the influence of obesity on clearance can be predicted on the basis of reported changes in the metabolic or elimination pathways involved. For obese children, we propose two methods to distinguish between developmental and obesity-related changes. Future research should focus on the characterization of physiological concepts to predict the optimal dose for each drug in the obese population.
language: eng
source:
identifier: ISSN: 0362-1642
fulltext: no_fulltext
issn:
  • 0362-1642
  • 1545-4304
url: Link


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descriptionObesity and morbid obesity are associated with many physiological changes affecting pharmacokinetics, such as increased blood volume, cardiac output, splanchnic blood flow, and hepatic blood flow. In obesity, drug absorption appears unaltered, although recent evidence suggests that this conclusion may be premature. Volume of distribution may vary largely, but the magnitude and direction of changes seem difficult to predict, with extrapolation on the basis of total body weight being the best approach to date. Changes in clearance may be smaller than in distribution, whereas there is growing evidence that the influence of obesity on clearance can be predicted on the basis of reported changes in the metabolic or elimination pathways involved. For obese children, we propose two methods to distinguish between developmental and obesity-related changes. Future research should focus on the characterization of physiological concepts to predict the optimal dose for each drug in the obese population.
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subjectAdministration, Oral ; Adolescent ; Adult ; Age Factors ; Aged ; Animals ; Biological Availability ; Body Mass Index ; Body Weight ; Child ; childhood ; children ; Drug Dosage Calculations ; Evidence-Based Medicine - methods ; Female ; Gastrointestinal Absorption ; Humans ; Male ; Middle Aged ; Models, Biological ; morbidly obese ; obese ; Obesity - diagnosis ; Obesity - metabolism ; Obesity - physiopathology ; Pharmaceutical Preparations - administration & dosage ; Pharmaceutical Preparations - metabolism ; pharmacodynamics ; Pharmacokinetics ; precision medicine ; prediction in pharmacology ; Tissue Distribution ; Young Adult
ispartofAnnual review of pharmacology and toxicology, 2015-01-06, Vol.55 (1), p.149-167
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abstractObesity and morbid obesity are associated with many physiological changes affecting pharmacokinetics, such as increased blood volume, cardiac output, splanchnic blood flow, and hepatic blood flow. In obesity, drug absorption appears unaltered, although recent evidence suggests that this conclusion may be premature. Volume of distribution may vary largely, but the magnitude and direction of changes seem difficult to predict, with extrapolation on the basis of total body weight being the best approach to date. Changes in clearance may be smaller than in distribution, whereas there is growing evidence that the influence of obesity on clearance can be predicted on the basis of reported changes in the metabolic or elimination pathways involved. For obese children, we propose two methods to distinguish between developmental and obesity-related changes. Future research should focus on the characterization of physiological concepts to predict the optimal dose for each drug in the obese population.
copUnited States
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pmid25340929
doi10.1146/annurev-pharmtox-010814-124354