Comparative pharmacokinetics of co-trifamole and co-trimoxazole to 'steady state' in normal subjects.

The plasma and urine concentrations of trimethoprim (TMP) and sulphonamide obtained using co-trimoxazole and co-trifamole (TMP and sulphamoxole) were estimated in 10 patients in a two way cross-over study using the manufacturers' recommended dosage schedules. The pharmacokinetics of TMP using either preparation were comparable with those reported elsewhere; as were the kinetics of sulphamethoxazole. The values obtained for sulphamoxole, not previously reported, were 8.0 ± 2.8 h, 0.096 ± 0.031 h, CL 0.9 ± 0.4 1h and 9.4 ± 2.01. Studies in plasma showed sulphamoxole to have a lower volume of distribution than sulphamethoxazole. The half-lives of the two did not differ significantly; steady state plasma concentrations were achieved more rapidly (≃25 h) for co-trifamole than for co-trimoxazole (≃49 h) as a result of the differences in recommended dosage schedule. Differences in urinary concentration of TMP and sulphonamide obtained using the two preparations were a reflection of the dosage regimens rather than the pharmacokinetics of the individual drugs. Urinary concentrations of TMP greatly exceeded the MIC for sensitive organisms in all cases. Sulphonamide concentrations fell below the MIC for both drugs and in neither case were optimum synergistic ratios obtained in urine. The figures obtained suggest that the use of sulphamoxole offers no advantage over sulphamethoxazole so far as the plasma and urinary concentrations are concerned, and suggest that in the treatment of urinary tract infections the necessity for combination therapy with TMP and a sulphonamide is open to question.