Rifaprim (rifampicin plus trimethoprim): pharmacokinetics and effects on the normal flora of man

Abstract

Ten healthy volunteers were given 'Rifaprim' in the dosage recommended for the treatment of urinary infections in man (rifampicin 300 mg + trimethoprim 80 mg in the morning and double these amounts at night, for 7 days). Levels of both drugs in the serum and urine were determined on the first and last days. The results show that trimethoprim was always present in the serum in amounts sufficient to suppress the emergence of resistance to rifampicin. In the urine, inhibitory concentrations of each drug were present throughout the course of treatment. Aerobic organisms were largely eliminated from the gut and reappeared after treatment still sensitive to both antibiotics: the anaerobic moiety persisted and became resistant to rifampicin. Changes in nasopharyngeal flora were relatively minor. Thus, this dosage regimen of "Rifaprim' contains enough trimethoprim to prevent the emergence of resistance to rifampicin among urinary pathogens under normal circumstances (i.e. provided the organisms are initially sensitive to trimethoprim).