Exploring the Pharmacokinetic Profile of Antiretroviral Efavirenz in Low Protein Malnourished Condition in Wistar Rats.

Background and objectives: The HIV infection in malnourished conditions raises the concerns with antiretroviral medications, which may worsen the already compromised physiological state. The alteration in the plasma protein binding in malnourished HIV patients exacerbates the unbound fraction of antiretroviral medications, resulting in alterations in the therapeutic effectiveness and toxicity. Thus, the present study investigates the effects of protein deficiency and protein-energy malnutrition on the pharmacokinetics of the antiretroviral efavirenz.

Method: Malnutrition was induced in this study through a modified diet containing only 2% protein. The experiment involved 16 Wistar rats, divided into two groups of 8. The control group was provided with a standard pellet diet (AIN 93G) that contained 19% protein, while the second group was subjected to the low-protein (2%) diet for 90 days. Rats were fed ad libitum with their respective diets during this period. On the 90th day, efavirenz (200 mg/kg, p.o.) was administered, and pharmacokinetic parameters were assessed using HPLC analysis.

Results: The findings indicate that the protein-deficient diet successfully created a model of malnutrition, evidenced by a significant reduction in body weight (26%), hemoglobin levels (33%), total protein (27%), and blood albumin (41%) compared to the control group on a standard diet. The pharmacokinetic analysis of efavirenz in the protein-deficient rats revealed an increase in half-life (T_½) by 51.27%, maximum concentration (C_max) by 31.57%, and area under the curve (AUC 0-∞) by 51.40%, alongside a decrease in total body clearance (45.81%) and volume of distribution (12.1%) relative to the pharmacokinetic profile observed in rats on the standard AIN 93G diet.

Conclusion: These findings indicate that the pharmacokinetic profile of efavirenz is significantly altered under protein-deficient conditions. Therefore, it is recommended that further pharmacokinetic studies be conducted in patients with protein deficiency to determine if standard dosing of efavirenz should be adjusted based on the individual's nutritional status.