Factors affecting drug pharmacokinetics in obesity^[1]

Volume of distribution

Increased fat mass

Increased lean body mass

Increased total body water

Increased blood volume

Increased cardiac output

Organomegaly

Protein binding*

Possible increased lipoproteins (eg, cholesterol or triglycerides)

Altered alpha1-acid glycoprotein

Drug metabolism

Increased activity of some CYP P450 enzymes^¶

Increased phase II drug metabolism via glucuronidation and sulfation

Excretion

Increased renal blood flow

Increased GFR

Increased renal tubular secretion and reabsorption

Individual organ system comorbid conditions

Pharmacokinetics for many drugs have not been well studied in obese patients, and depend on the degree of lipophilicity or hydrophilicity, protein binding, and mechanisms of metabolism and excretion. The increased volume of distribution can prolong the half-life of elimination, particularly for lipophilic drugs and prolonged infusion, despite increased drug clearance. Alterations in body composition and physiologic parameters vary with the degree of obesity, and may be affected by comorbidities that are commonly associated with obesity (eg, diabetes mellitus, hypertension, cardiovascular disease, fatty liver disease) or other etiologies.

CYP: cytochrome; GFR: glomerular filtration rate.
* The effects of obesity on various plasma proteins have not been well established, and may vary among patients. Serum albumin is generally unchanged in obesity.
¶ Effects of obesity on the CYP enzymes is variable among the different enzymes. Obesity increases activity of CYP2E1, but studies on the effects of obesity on other isozymes are inconsistent.

Reference:

Shenkman Z, Shir Y, Brodsky JB. Perioperative management of the obese patient. Br J Anaesth 1993; 70:349.

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Factors affecting drug pharmacokinetics in obesity[1]

Factors affecting drug pharmacokinetics in obesity^[1]