Effect of Trimethoprim on Lamivudine Bioavailability-Reply

In Reply.  —Trimethoprim increases the lamivudine area-under-the-curve (AUC) because of competition for renal excretion through the organic cationic transport system in the kidneys. While it is tempting to consider lower doses of lamivudine in combination with trimethoprim to reduce the cost of antiretroviral regimens, this approach is inappropriate because the bioavailability of lamivudine has a high interpatient variability (mean, 86%; range, 53%-105%),¹ and the interpatient variability for the lamivudine AUC when it is administered with trimethoprim-sulfamethoxazole is also high at 44% (SD, 23%).²Monitoring blood levels of lamivudine to ensure adequate exposure to the drug would outweigh the benefits of a simple oral dosing regimen. Moreover, the clearance of other medications that are renally excreted by the organic cationic transport system would be affected by the routine use of trimethoprim to enhance lamivudine levels. While the increased blood levels of lamivudine are not associated with any increased risk of adverse