DRUG PHARMACOKINETICS IN THE OBESE
Identifieur interne : 000B56 ( Main/Merge ); précédent : 000B55; suivant : 000B57DRUG PHARMACOKINETICS IN THE OBESE
Auteurs : G. Cheymol [France]Source :
- Fundamental & Clinical Pharmacology [ 0767-3981 ] ; 1988-12.
English descriptors
- Teeft :
- Abernethy, Abernethy greenblatt, Abernethy greenblatt divoll, Adipose, Adipose storage index, Adipose tissue, Adipose tissue storage, Adipose tissues, Antipyrine, Arterial hypertension, Arthritis rheum, Bauer, Benedek, Benzodiazepine, Blood flow, Blood volume, Body weight, Caffeine, Cardiac, Cardiac output, Cheymol, Clearance, Clin, Control group, Control subjects, Digoxin, Distribution volume, Drug diffusion, Drug disposition, Drug distribution, Drug elimination, Drug pharmacokinetics, Excess weight, Fatty tissue, Fatty tissues, Glycoprotein acid, Greenblatt, Hepatic, Hepatic blood flow, Hepatic clearance, Hepatic metabolism, Hydrophilic drugs, Ideal body weight, Ideal weight, Lean mass, Lean tissue, Lean tissues, Lipophilic, Lipophilic drugs, Lipophilic molecules, Loading dose, Lower percentage, Maintenance dose, Metabolic clearance, Methyl xanthines, Nonobese subjects, Normal volunteers, Normal weight, Obese, Obese body, Obese patients, Obese subjects, Obese table, Obese women, Obesity, Oral clearance, Pharmacokinetic, Pharmacokinetic parameters, Pharmacokinetic studies, Pharmacokinetics, Pharmacol, Plasma binding, Plasma elimination, Positive correlation, Principal elimination route, Propranolol, Propranolol binding, Protein binding, References abernethy, Regional blood flow, Renal, Renal elimination, Significant difference, Significant increase, Significant modifications, Single dose, Skinfold thickness, Table viii, Theophylline, Thiopental, Tissue distribution, Total blood flow, Total blood volume, Total body weight, Total clearance, Total distribution volume, Total plasma clearance, Total weight, Urinary excretion, Various types.
Abstract
Summary— In the obese, modifications in body constitution (higher percentage of fat and lower percentage of lean tissue and water) can affect drug distribution in the tissues. For slightly liposoluble molecules (e.g., digoxin, antipyrine), the equilibrium distribution volume (V), total and per kilogram weight, is significantly less than that of control subjects. With lipophilic drugs (e.g., barbiturates, benzodiazepines), this parameter is significantly increased, explaining the prolongation of the plasma elimination half‐life. For drugs that are almost equally soluble in water and oil (methyl xanthines, aminoglycosides), the V is slightly increased in the obese.
The other main factors involved in drug diffusion in the tissues are binding to plasma and tissue proteins, and regional blood flow. In the obese the binding of drugs to albumin does not seem to be altered. A marked increase in plasma α‐glycoprotein acid and in propranolol binding has been reported in some studies; this has not been corroborated by other authors. Although the cardiac output and total blood volume are increased in the obese, the blood flow per gram of fat is less than in nonobese subjects. This could limit diffusion in the tissues of some lipophilic drugs. Studies on hepatic clearance of drugs are not available in the obese, but hepatic histological alterations have been described. In most publications concerning drugs with biotransformation as the principal elimination route, the total plasma clearance is not reduced. Up to the present, there are no reports of any impairment involving renal elimination of drugs in the obese.
Dose‐adjustment of hydrophilic drugs is assessed according to the ideal weight of the individual obese subject; with lipophilic drugs the loading dose can be fixed according to the total weight; calculation of the maintenance dose depends on possible changes in the total clearance.
Url:
DOI: 10.1111/j.1472-8206.1988.tb00664.x
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<profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Abernethy</term>
<term>Abernethy greenblatt</term>
<term>Abernethy greenblatt divoll</term>
<term>Adipose</term>
<term>Adipose storage index</term>
<term>Adipose tissue</term>
<term>Adipose tissue storage</term>
<term>Adipose tissues</term>
<term>Antipyrine</term>
<term>Arterial hypertension</term>
<term>Arthritis rheum</term>
<term>Bauer</term>
<term>Benedek</term>
<term>Benzodiazepine</term>
<term>Blood flow</term>
<term>Blood volume</term>
<term>Body weight</term>
<term>Caffeine</term>
<term>Cardiac</term>
<term>Cardiac output</term>
<term>Cheymol</term>
<term>Clearance</term>
<term>Clin</term>
<term>Control group</term>
<term>Control subjects</term>
<term>Digoxin</term>
<term>Distribution volume</term>
<term>Drug diffusion</term>
<term>Drug disposition</term>
<term>Drug distribution</term>
<term>Drug elimination</term>
<term>Drug pharmacokinetics</term>
<term>Excess weight</term>
<term>Fatty tissue</term>
<term>Fatty tissues</term>
<term>Glycoprotein acid</term>
<term>Greenblatt</term>
<term>Hepatic</term>
<term>Hepatic blood flow</term>
<term>Hepatic clearance</term>
<term>Hepatic metabolism</term>
<term>Hydrophilic drugs</term>
<term>Ideal body weight</term>
<term>Ideal weight</term>
<term>Lean mass</term>
<term>Lean tissue</term>
<term>Lean tissues</term>
<term>Lipophilic</term>
<term>Lipophilic drugs</term>
<term>Lipophilic molecules</term>
<term>Loading dose</term>
<term>Lower percentage</term>
<term>Maintenance dose</term>
<term>Metabolic clearance</term>
<term>Methyl xanthines</term>
<term>Nonobese subjects</term>
<term>Normal volunteers</term>
<term>Normal weight</term>
<term>Obese</term>
<term>Obese body</term>
<term>Obese patients</term>
<term>Obese subjects</term>
<term>Obese table</term>
<term>Obese women</term>
<term>Obesity</term>
<term>Oral clearance</term>
<term>Pharmacokinetic</term>
<term>Pharmacokinetic parameters</term>
<term>Pharmacokinetic studies</term>
<term>Pharmacokinetics</term>
<term>Pharmacol</term>
<term>Plasma binding</term>
<term>Plasma elimination</term>
<term>Positive correlation</term>
<term>Principal elimination route</term>
<term>Propranolol</term>
<term>Propranolol binding</term>
<term>Protein binding</term>
<term>References abernethy</term>
<term>Regional blood flow</term>
<term>Renal</term>
<term>Renal elimination</term>
<term>Significant difference</term>
<term>Significant increase</term>
<term>Significant modifications</term>
<term>Single dose</term>
<term>Skinfold thickness</term>
<term>Table viii</term>
<term>Theophylline</term>
<term>Thiopental</term>
<term>Tissue distribution</term>
<term>Total blood flow</term>
<term>Total blood volume</term>
<term>Total body weight</term>
<term>Total clearance</term>
<term>Total distribution volume</term>
<term>Total plasma clearance</term>
<term>Total weight</term>
<term>Urinary excretion</term>
<term>Various types</term>
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<front><div type="abstract">Summary— In the obese, modifications in body constitution (higher percentage of fat and lower percentage of lean tissue and water) can affect drug distribution in the tissues. For slightly liposoluble molecules (e.g., digoxin, antipyrine), the equilibrium distribution volume (V), total and per kilogram weight, is significantly less than that of control subjects. With lipophilic drugs (e.g., barbiturates, benzodiazepines), this parameter is significantly increased, explaining the prolongation of the plasma elimination half‐life. For drugs that are almost equally soluble in water and oil (methyl xanthines, aminoglycosides), the V is slightly increased in the obese.</div>
<div type="abstract">The other main factors involved in drug diffusion in the tissues are binding to plasma and tissue proteins, and regional blood flow. In the obese the binding of drugs to albumin does not seem to be altered. A marked increase in plasma α‐glycoprotein acid and in propranolol binding has been reported in some studies; this has not been corroborated by other authors. Although the cardiac output and total blood volume are increased in the obese, the blood flow per gram of fat is less than in nonobese subjects. This could limit diffusion in the tissues of some lipophilic drugs. Studies on hepatic clearance of drugs are not available in the obese, but hepatic histological alterations have been described. In most publications concerning drugs with biotransformation as the principal elimination route, the total plasma clearance is not reduced. Up to the present, there are no reports of any impairment involving renal elimination of drugs in the obese.</div>
<div type="abstract">Dose‐adjustment of hydrophilic drugs is assessed according to the ideal weight of the individual obese subject; with lipophilic drugs the loading dose can be fixed according to the total weight; calculation of the maintenance dose depends on possible changes in the total clearance.</div>
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