Clinical Pharmacokinetics of Co-Trimazine

Abstract

The clinical pharmacokinetics of co-trimazine (trimethoprim plus sulphadiazine) are reviewed and compared with those of co-trimoxazole (trimethoprim plus sulphamethoxazole). Both combination drugs have similar serum half-life values in persons with normal renal function (half-life of 8 to 12 hours), but the sulphamethoxazole metabolites are retained more than trimethoprim in reduced renal function. Sulphadiazine is less metabolised and the total sulphonamide load of therapeutic doses of co-trimazine is therefore less than for co-trimoxazole. Both co-trimazine and co-trimoxazole have high bioavailability. A suspension of co-trimazine gives serum concentrations comparable with those of tablets. The extravascular penetration of the co-trimazine components is reflected by the total area under the lymph concentration curve in comparison with serum. This measure shows a penetration into peripheral human lymph of 68% for sulphadiazine and 59% for trimethoprim. The proportions eliminated in urine are about 55% for sulphadiazine, 30% for its acetylated metabolite and 75% for trimethoprim. In comparison, for co-trimoxazole, the proportion of sulphamethoxazole eliminated in urine is 15%, that of the acetylated derivative 47%, and that of trimethoprim is also 75%. Urine concentrations of both combinations have similar bioactivity against urinary pathogens after 500 mg of co-trimazine and 960 mg of co-trimoxazole.