Abstract
The distributions of trimethoprim (TMP) and nonacetylated sulfamethoxazole (SMZ) were studied in tissues of rhesus monkeys at equilibrium after establishment of serum levels comparable to those in man. Concentrations of nonacetylated SMZ in tissue were always lower than those in serum, with the highest concentrations in kidney, lung, and heart. In contrast, concentrations of TMP in tissue were greater than those in serum, except in brain, skin, and fat. The greatest uptake of TMP by tissues was observed in kidney and liver. The ratio of SMZ to TMP was significantly less in tissue than in serum and was lower than the optimal 20:1 ratio for antibacterial synergy. The rate of disappearance of both drugs from tissues was identical to their rate of elimination from serum. The pharmacokinetics of trimethoprim (TMP) and sulfamethoxazole (SMZ) in animals and man have been previously reported [1-3]. Calculations of distribution have suggested significant uptake of TMP but not of SMZ by tissues. Biopsy material from patients and distribution studies in tissues of the rat, mouse, and rabbit have shown that the concentration of TMP in tissues exceeds that in serum, whereas levels of SMZ are lower in tissues than in serum [3-5]. We designed the following investigations to determine the distribution of these drugs in the tissues of primates at equilibrium with serum levels comparable to those in man.
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