Human pharmacokinetics of a sulfamethoxazole-trimethoprim combination.

Abstract

Abstract The pharmacokinetic characteristics of the fixed chemotherapeutic combination of sulfamethoxazole (SMZ) and trimethoprim (TMP) have been elucidated in 14 patients with different renal functions. The peak serum concentrations (cmax) after two tablets totalling 160 mg TMP and 800 mg SMZ in patients with creatinine clearances (Cer) above 60 ml/min were around 40 μg/ml for potentially antibacterial SMZ; the non‐active SMZ metabolites in addition contributed another 10 μg/ml. The TMP peak values averaged 1.4 μg/ml in serum. In patients with renal insufficiency the cmax was lower. Serum half‐life (t1/2) of active SMZ (SMZa) was 7 hours normally and only slightly changed with impaired kidney function. The t1/2 for total SMZ (SMZt) and TMP, however, normally 12 and 13 hours respectively, were increased in patients with reduced Ccr values. This increase was most marked for SMZt. The t1/2 of SMZt began to increase around Ccr=30 ml/min, t1/2 of TMP only at around 20 ml/min. In addition to similarities between SMZ and TMP excretion rates in normal persons, invasion phase kinetics of both compounds were of the same order. The distribution coefficient, however, was close to 2.0 for TMP, but only 0.2 for total and 0.3 for active SMZ. In patients with Ccr above 60 ml/min, 4–5.5 hour urine samples exhibited a mean SMZa concentration of 29.5 μg/ml and a TMP concentration of 78.4 μg/ml. There were approximately 15 times more non‐active SMZ metabolites than SMZa. All components appeared in lesser urine concentrations in renal insufficiency.