Author:
Trottier S,Bergeron M G,Lessard C
Abstract
In the present study, rats were given trimethoprim (TMP, 10 mg/kg), sulfamethoxazole (SMZ, 50 mg/kg), or a combination of the respective doses of TMP and SMZ. Thirty-six rats received each of the drugs studied. Six recipients of a compound (or mixture) were evaluated hourly, from 1 to 6 h after intraperitoneal injection of the agent. At each timed interval, serum, urine, cortex, medulla, and papilla were analyzed for drug content. Peak serum values of 1.1 microgram of TMP and 131.1 microgram of active SMZ (nonacetylated sulfonamide) per ml were observed after injection of the combination TMP-SMZ. Although the cortical, medullary, and papillary TMP concentrations were severalfold higher than the respective serum values (P < 0.01), microbiologically active SMZ did not concentrate in the renal parenchyma and was found in lower concentration there than in the serum (P < 0.01). The levels of SMZ in all parts of the kidney of animals which received the mixture SMZ-TMP were lower than those detected in the animals which were given SMZ alone. The average ratio of active SMZ to TMP within the medulla and the papilla was less than 20 to 1 in the first 2 h. The intrarenal distribution of these drugs may have therapeutic implications.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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