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

Author:

Watson I D1,Stewart M J1,Wiles A1,McIntosh S J1

Affiliation:

1. Drug Investigation Unit, Department of Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland

Abstract

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 disposition of higher TMP concentrations following the initial dose of the 300 mg preparation is reversed when steady-state is reached, and is a function of dosage. The MIC of TMP for sensitive organisms in urine was greatly exceeded following both regimens and is the result of 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 treatment of urinary tract infection the 200 mg regimen would be more appropriate for the treatment of infected sites where pH dependent accumulation of TMP does not occur.

Publisher

SAGE Publications

Subject

Biochemistry, medical,Cell Biology,Biochemistry,General Medicine

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