Bioavailability of a Combination Preparation of Trimethoprim and Folic Acid

Abstract

The bioavailability of folic acid and trimethoprim was investigated from a combination preparation of folic acid (0·25 mg) and trimethoprim (100 mg) in ten healthy adult volunteers. Peroral administration of the preparation resulted in a mean peak plasma concentration of trimethoprim 1·09 mg/l (SEM 0·06). The AUC values for trimethoprim were 12·42 mg.h/l and 12·77 mg.h/l corresponding to combination preparation and plain trimethoprim, p >0·1. After administration 0·25 mg folic acid in the combination preparation, there was a significant rise in serum folic acid concentrations. The AUC from 0–8 hours was 199·8 nmol.h/l (SEM 8·1) and 166·3 nmol.h/l (SEM 14·2) corresponding to combination preparation and plain trimethoprim, p < 0·001. A loading dose of folic acid 10 mg was given intramuscularly 24 hours before drug intake. This new type of formulation of trimethoprim and folic acid has been developed in order to prevent in long-term use the adverse haematological effects induced by trimethoprim alone.