[Bone diffusion of trimethoprim and sulfamethoxazole high pressure liquid chromatography (HPLC) (author's transl)]

Fourteen patients about to undergo total hip prosthesis were given 640 mg TMP and 3.2 g SMZ during the 48 hours previous to surgical procedure. Ten ml blood, fragments of cortical bone, spongy bone and bone marrow were taken 1 h to 1 h 30 mn after the last drug intake. Dosage were made using HPLC after biological specimens had been treated on a TM C18 Set Pack column for deproteinization and isolation of the active substances. Results show high mean serum levels, 7.73 micrograms/ml for TMP and 143.82 micrograms/ml for SMZ. Whatever the bone specimen be, diffusion of TMP was excellent, with levels between 2.20 and 4.96 microgram/g whereas SMZ levels were between 13.85 and 23.85 microgram/g. For each sample, the TMP/SMZ ratio was the following : in serum it was equal to 0.055, which is in accordance with results already published ; the ratio between the levels of the two active substances was more favourable for cortical bone (ratio = 0.185) than for spongy bone (ratio = 0.286) or bone marrow (ratio = 0.324). The bone level/serum level ratio shows a diffusion which is two to six times greater for TMP than for SMZ in all bone specimens : TMP penetrates marrow better than it does cortical and spongy tissues ; diffusion is practically equivalent in the two latter tissues ; SMZ concentrates very strongly in the marrow and not so well in the cortical and the spongy bones.