Pharmacokinetic study of a sulfametopyrazine/trimethoprim combination (Kelfiprim) in human volunteers.

Abstract

The pharmacokinetics of a combination of sulfametopyrazine (SMP) and trimethoprim (TMP) were studied following their daily oral administration to six healthy volunteers. In an initial study a loading dose of three times the daily maintenance dose of SMP 200 mg plus TMP 250 mg was used in a cross-over study with the individual drugs. No significant interference of drug absorption was observed using the combination as opposed to its components alone. In some subjects the triple loading dose resulted in higher peak blood levels of TMP. Thus in a second study a loading dose of only twice the maintenance dose was used; dosing was continued for 10 days, and blood and urine concentrations were monitored for 14 days. The pharmacokinetic characteristics of SMP and TMP resembled those described in other studies; the mean terminal plasma half lives were 70 and 11 h, respectively. The urinary excretion of active SMP was nearly 20%, and that of TMP nearly 60%. Using the double loading dose the final steady-state blood concentrations of SMP (nadir 50 mg/l; peak 65 mg/l) and TMP (nadir 1.1 mg/l; peak 3.3 mg/l) were achieved on the seventh and third days of dosing, respectively. It was concluded that the double loading dose represented the best compromise considering the differing pharmacokinetics of two antimicrobials, if a fixed ratio and dosage size were to be used.