title: 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 < or = 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 function but is likely to further inhibit cationic tubular secretion in patients on tacrolimus therapy.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, PA 15261, USA.
authors.forename: S
authors.initials: S
authors.lastname: Agarwala
authors.forename: J
authors.initials: J
authors.lastname: Ou
authors.forename: V
authors.initials: V
authors.lastname: Subbotin
authors.forename: S
authors.initials: S
authors.lastname: Zuckermann
authors.forename: P
authors.initials: P
authors.lastname: Randhawa
authors.forename: G
authors.initials: G
authors.lastname: Burckart
authors.forename: R
authors.initials: R
authors.lastname: Venkataramanan
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D016559:Tacrolimus