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  • Title: Influence of obesity on drug disposition.
    Author: Blouin RA, Kolpek JH, Mann HJ.
    Journal: Clin Pharm; 1987 Sep; 6(9):706-14. PubMed ID: 3315402.
    Abstract:
    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 correlate with drug lipophilicity. Drugs that have a high affinity for adipose tissue have an increased volume of distribution, whereas the distribution of drugs that have low partition coefficients is not altered substantially. Albumin and total protein concentrations are comparable in lean and obese subjects, but concentrations of alpha 1-acid glycoprotein are increased. Consequently, protein binding of acidic drugs is unchanged, but the free fraction of basic drugs may be decreased. Changes in hepatic drug clearance are complex. Phase 1 reactions and acetylation, a Phase 2 reaction, appear to be unaffected by obesity, but activity of Phase 2 glucuronidation and sulfation pathways is enhanced. Available physiologic and pharmacokinetic data on the effect of obesity on systemic clearance of highly extracted drugs are conflicting. Both glomerular filtration and tubular secretion appear to be increased in obese individuals, and tubular secretion may be disproportionately increased compared with filtration. Clearance of drugs that depend on glomerular filtration for elimination is consistently higher in obese subjects. Differences among patient populations, other conditions associated with obesity, and the small study populations described to date may account for some discrepancies in reported results. Awareness of the physiologic effects of obesity is essential for ensuring appropriate drug therapy in obese patients.
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