13.9: Pharmacokinetics in Obese Patients: Drug Absorption and Distribution

Obesity significantly alters the pharmacokinetic processes of drug absorption and distribution, presenting unique challenges in medical treatment. The increased fat tissue and decreased lean muscle in obese individuals can significantly affect how drugs are absorbed into the body and distributed across different tissues. This alteration can lead to variances in the effectiveness and safety of medications, necessitating adjustments in dosing or drug selection for obese patients.

One notable example of these pharmacokinetic changes involves the diabetes medication metformin. A comparative study examined the bioavailability of metformin between patients who had undergone gastric bypass surgery and those with a similar body mass index (BMI) who had not. The findings revealed that post-surgery patients exhibited a 50% increase in metformin's bioavailability, indicating that surgical modifications to the gastrointestinal tract can dramatically influence drug absorption and efficacy.

The distribution of drugs within the body is also influenced by the individual's body composition and the chemical nature of the drug. Drugs are categorized based on their lipophilicity or fat solubility. In obese patients, lipophilic drugs tend to have an increased volume of distribution, meaning they spread more extensively into fat tissues. Conversely, hydrophilic drugs, which are water-soluble, show a lesser increase in distribution volume in obese individuals compared to their non-obese counterparts. Surprisingly, certain lipophilic drugs, such as cyclosporine, demonstrate a reduced volume of distribution in obese patients, highlighting the complexity of drug pharmacokinetics in varied body compositions.

Moreover, obesity can influence the concentration of plasma binding proteins, such as α1-acid glycoprotein, which bind to drugs in the bloodstream, affecting the proportion of the unbound and active drug. These changes necessitate a careful consideration of drug dosing and choice in treating obese patients, underlining the importance of personalized medicine in this population. The interplay between obesity, drug absorption, distribution, and the role of plasma proteins underscores the critical need for targeted research and clinical strategies to optimize therapeutic outcomes for obese individuals.

Obese individuals typically have more fat tissue and less lean tissue, which impacts drug absorption and distribution. However, available data are limited.

For example, the bioavailability of metformin was compared between individuals who underwent gastric bypass surgery and those who did not, with both groups having a similar BMI.

The results showed a 50% increase in metformin bioavailability after gastric bypass surgery compared to the nonsurgery cohort.

Drug distribution in obese individuals is affected by increased adipose tissue and the drugs’ lipophilicity.

For instance, lipophilic drugs show an increased V_D and prolonged half-life compared to hydrophilic drugs, which exhibit a lesser V_D.

However, certain lipophilic drugs, such as cyclosporine, have a lower V_D in obese patients than in non-obese patients.

Additionally, obesity can alter the concentrations of plasma proteins such as α₁-acid glycoprotein, affecting the unbound drug fraction. For instance, an increase in protein concentration can decrease the unbound drug concentration.