Sulfamethoxazole and trimethoprim are well-absorbed orally, reaching peak plasma concentrations within 1-4 hours. Food slightly delays absorption but doesn’t significantly affect the extent of absorption. This makes administration convenient for patients.
Distribution
Both drugs distribute widely throughout the body’s fluids and tissues, including cerebrospinal fluid (CSF), although penetration into the CSF is limited. High concentrations are found in the kidneys, lungs, liver, and spleen. Protein binding varies, with approximately 66% of sulfamethoxazole bound to plasma proteins and around 45% of trimethoprim.
Metabolism
Sulfamethoxazole undergoes hepatic metabolism, primarily via acetylation, producing inactive metabolites excreted in urine. Trimethoprim’s metabolism is more complex, involving oxidation and conjugation, producing a mixture of metabolites with varying degrees of activity. The primary route of excretion for both drugs is the kidneys.
Excretion
Renal excretion is the major elimination pathway for both components. Approximately 50-70% of sulfamethoxazole and its metabolites are excreted unchanged in the urine. Trimethoprim excretion occurs primarily as unchanged drug and metabolites, with approximately 30-60% appearing unchanged in the urine. Patients with impaired renal function require dose adjustments to prevent drug accumulation and potential toxicity. Careful monitoring of renal function is recommended during treatment. Adjustments should be based on creatinine clearance.
Drug Interactions
Concurrent use with other medications may lead to interactions. For example, competitive inhibition of tubular secretion can occur, affecting the excretion of other drugs. This interaction is particularly relevant for drugs such as methotrexate, which might increase toxicity when co-administered with sulfamethoxazole/trimethoprim.
