Co-administration of Co-trimoxazole Does Not Augment Tacrolimus-Induced Impairment in Kidney Function in Rats

Abstract

Co-trimoxazole is an antibiotic that is frequently used in organ transplant patients. Our objective was to determine the effect of co-trimoxazole on tacrolimus-mediated functional impairment of the kidney in rats. Sprague Dawley rats were divided into three groups. Group 1 (dextrose) received 5% dextrose and Group 2 (tacrolimus) received tacrolimus (1 mg/kg/day) as a continuous intravenous infusion for seven days. Group 3 (combination) received tacrolimus as above and co-trimoxazole (30 mg/kg/day trimethoprim and 150 mg/kg/day sulfamethoxazole) intraperitoneally for six or seven days. Biochemical and functional parameters were measured pre- and post-drug infusion. On day 7, glomerular filtration rate (GFR) was evaluated using ³H-inulin. while the effective renal plasma flow (ERPF)/cationic tubular secretion was assessed using ¹⁴C-tetraethylammoniumbromide (TEA).

GFR (mL/min/kg) as measured by inulin clearance was higher (p ≤ 0.05) in the dextrose (12.0 ± 1.4) group as compared to tacrolimus group (6.0 ± 1.3) and combination group (6.4 ± 1.6), but there was no difference between the tacrolimus and combination group. ERPF/cationic tubular secretion (mL/min/kg) was also significantly higher in the dextrose group (62.6 ± 10.3) as compared to the other two groups. ERPF/cationic tubular 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 the body. However, in the presence of co-trimoxazole ERPF/cationic tubular secretion 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 tacrolimus induced impairment in kidney Junction but is likely to further inhibit cationic tubular secretion in patients on tacrolimus therapy.

Key Words:

• Co-trimoxazole
• Tacrolimus
• GFR
• TEA
• Nephrotoxicity
• Rats