Pharmacokinetics of Two Dosage Levels of Trimethoprim to ‘Steady-State’ in Normal Volunteers

Trimethoprim (TMP), previously available only with a sulphonamide. is now available alone. The kinetics of two dosage regimens (200 mg b.d. p.o. and 300 mg o.d. p.o.) have been examined. The expected dispositionof higher TMP concentrations following the initial doseof the 300 mg preparation is reversed whensteady-state is reached, and isafunction ofdosage. The MIC of TMP for sensitive organisms in urine was greatly exceeded following both regimens and is the resultof a favourable pH gradient. The serum concentrations at Css (trough) following the 300 mg regimen did not consistently exceed the MIC for TMP, those for the 200 mg regimen were more satisfactory. The implications of these findings are that while both regimens would be satisfactory in the treatmentofurinary tract infection the 200 mg regimen would be more appropriate for the treatmentofinfected sites wherepHdependent accumulationofTMPdoes not occur.