Co-administration of co-trimoxazole does not augment tacrolimus-induced impairment in kidney function in rats

Co-trimoxazole is an antibiotic that is frequently used in organ transplant patients. Our objective was to determine the effect of co-trimoxazole on t acrolimus-mediated functional impairment of the kidney in mts. Sprague Dawl ey rats were divided into three groups. Group 1 (dextrose) received 5% dext rose and Group 2 (tacrolimus) received tacrolimus (I mg/kg/day) as a contin uous intravenous infusion for seven days. Group 3 (combination) received ta crolimus as above and co-trimoxazole (30 mg/kg/day trimethoprim and 150 mg/ kg/day sulfamethoxazole) intraperitoneally for six or seven clays. Biochemi cal and functional parameters were measured pre- and post-drug infusion. On day 7, glomerular filtration rate (GFR) was evaluated using H-3-inulin, wh ile the effective renal plasma flow (ERPF)/cationic tubular secretion was a ssessed using C-14-tetraethylammoniumbromide(TEA). GFR (mL/min/kg) as measured by inulin clearance was higher (p less than or equal to 0.05) in the dextrose (12.0 +/- 1.4) group as compared to tacrolim us group (6.0 +/- 1.3) and combination group (6.4 +/- 1.6), but there was n o difference between the tacrolimus and combination group. ERPF/cationic tu bular secretion (mL/min/kg) was also significantly higher in the dextrose g roup (62.6 +/- 10.3) as compared to the other two groups. ERPF/cationic tub ular secretion was not different between the combination (33.3 +/- 5.9) and the tacrolimus (35.1 +/- 6.7) groups when there was no co-trimoxazole in t he body. However, in the presence of co-trimoxazole ERPF/cationic tubular s ecretion was significantly reduced in the combination (23.1 +/- 3.5) group as compared to the tacrolimus group (35.1 +/- 6.7). These results indicate that co-trimoxazole does not further potentiate tacr olimus induced impairment in kidney function hut is likely to further inhib it cationic tubular secretion in patients an tacrolimus therapy.