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

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Abstract
The plasma and urine concentrations of trimethoprim (TMP) and sulfonamide obtained using co-trimoxazole and co-trifamole (TMP and sulfamoxole) were estimated in 10 patients in a 2 way cross-over study using the manufacturers'' recommended dosage schedules. The TMP pharmacokinetics using either preparation were comparable with those reported elsewhere, as were the sulfamethoxazole kinetics. The values obtained for sulfamoxole, not previously reported, were serum half-life [t1/2] 8.0 .+-. 2.8 h, serum elimination rate constant 0.096 .+-. 0.031 h-1, serum clearance 0.9 .+-. 0.4 lh-1 and apparent volume of distribution 9.4 .+-. 2.0 l. Studies in plasma showed sulfamoxole to have a lower volume of distribution than sulfamethoxazole. The t1/2 of the 2 did not differ significantly; steady state plasma concentrations were achieved more rapidly (.apprx. 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 sulfonamide obtained using the 2 preparations reflected the dosage regimens rather than the pharmacokinetics of the individual drugs. Urinary concentrations of TMP greatly exceeded the MIC [minimum inhibitory concentrations] for sensitive organisms in all cases. Sulfonamide concentrations fell below the MIC for both drugs and in neither case were optimum synergistic ratios obtained in urine. Thus, the use of sulfamoxole offers no advantage over sulfamethoxazole in terms of the plasma and urinary concentrations. In the treatment of urinary tract infections, the necessity for combination therapy with TMP and a sulfonamide is open to question.

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