Pharmacokinetic changes of oral sulfamethoxazole in rabbits with diabetes mellitus induced by alloxan.
Because physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics of the drugs used to treat infectious diseases resulting from diabetic complications, the pharmacokinetics of sulfamethoxazole (sulfamethoxazole is usually used to treat secondary infectious diseases resulting from diabetic mellitus) were investigated after oral administration of the drug (50 mg/kg) to control rabbits and rabbits with acute (experiment was performed at fifth day after two consecutive days intravenous administration of alloxan) and chronic (experiment was performed at thirteenth day after first, second, sixth, and tenth days intravenous administration of alloxan) diabetes mellitus induced by alloxan. Impaired kidney and liver functions were observed in acute and chronic diabetes mellitus groups based on plasma chemistry data, and liver and kidney microscopy. After oral administration of sulfamethoxazole to acute and chronic groups, the plasma concentrations tended to be higher and this resulted in a significantly greater area under the plasma concentration-time curve from time zero to time infinity, AUC (6001 and 3867 compared with 1569 microg h/ml). This could be due to significantly slower (2-3 times) renal clearance because of impaired kidney function. The effects of diabetes on the pharmacokinetics of oral sulfamethoxazole were more considerable in acute group; the AUC and the maximum plasma concentration were significantly greater and higher, respectively, than those in control and chronic groups. After oral administration, some pharmacokinetic parameters of sulfamethoxazole were significantly different in diabetes mellitus.
Choi
J S
JS
College of Pharmacy, Chosun University, Dong-Gu, Kwangju, South Korea. jsachoi@mail.chosun.ac.kr
Choi
B C
BC
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D006207:Half-Life; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D011817:Rabbits; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D013420:Sulfamethoxazole