Showing papers by "Gordon L. Amidon published in 1973"
TL;DR: A dosage regimen involving reduced doses of both drugs, with an interval between doses of approximately 12 hr, is proposed for patients with severe renal failure.
Abstract: The pharmacokinetics of trimethoprim (TMP) and sulfamethoxazole (SMZ) were studied in subjects with normal and impaired renal function after single doses of the drugs administered separately and in combination. Serum levels and urinary excretion of TMP and free and conjugated SMZ were fitted to appropriate pharmacokinetic models by nonlinear least-squares methods. Neither drug influenced the pharmacokinetics of the other, and the acid and alkaline loading used did not markedly affect the clearance of either drug from serum. Rates of elimination and urinary concentrations of both drugs were significantly reduced in uremic subjects. Levels of SMZ in serum were slightly lower in uremic than in normal subjects. Levels of TMP in serum were similar in both groups but tended to be higher in uremic subjects from 5 hr after dosing. Distribution of free SMZ in tissues increased during renal insufficiency, probably due to reduced binding to serum proteins, whereas distribution of TMP in tissues showed little apparent change. A dosage regimen involving reduced doses of both drugs, with an interval between doses of approximately 12 hr, is proposed for patients with severe renal failure.
72 citations