Distribution of trimethoprim and sulphamethoxazole in blood during treatment with co-trimoxazole.

Changes in the distribution of sulphamethoxazole and trimethoprim in whole blood, plasma and erythrocytes at steady-state in patients treated with cotrimoxazole have been studied. Unlike sulphamethoxazole, trimethoprim was weakly bound to erythrocytes and was partially liberated when the erythrocytes were rinsed with isotonic saline. The maximal steady-state concentration of trimethoprim in whole blood was 3 mg/l, but calculated on the basis of the concentration determined in erythrocytes it was 1.8 mg/l. Erythrocytes may be of great significance in trimethoprim distribution as carriers of a readily liberated reservoir of the drug. Acetylated sulphamethoxazole derivatives occurred in a higher percentage in erythrocytes at the maximal steady-state concentration (9.9%) than at the level (7.3%), which may help in interpreting the behaviour of this metabolite in other cells in the organism.