The pharmacokinetics of DA-125 were compared after intravenous (i.v.) administration of the drug, 10 mg kg-I, to control male Sprague-Dawley rats ( n = 9) and uranyl nitrateinduced acute renal failure (U-ARF, n = 12) rats, or male SpragueDawley rats fed on a 23% (control, n = 8) or a 5% (protein-caloriemalnutrition, PCM, n = 9) protein diet. After i.v. administration of DA-125, almost 'constant' plasma concentrations of M1, M2, and M4 weremaintained from 1-2 h to 8-10 h in all rat groups due to thecontinuous formation of M2 from M1 and M4 from M3. The plasma concentrations of M3 were the lowest among Ml-M4 for all rat groups due to the rapid and almost complete conversion of M3 to M4 and other metabolite(s). The AUC, values of M1 (1 15 against 82.5 pgmin mL-I), M2 (33.0 against 23.6pgminmL-'), and M4 (26.3 against 15.1 pgminmL-') were significantly higher in the U-ARF rats than in the control rats. The percentages of i.v. dose excreted in 24 h urine as M1 (under the detection limit against 0.316%), M2 (under the detection limit against 5.58%), and M4 (0.0174 against 0.719%)-expressed in terms of DA-125-were significantly lower in the U-ARF rats than in the control rats, and this could be due to the decreased kidney function in the U-ARF rats. However, the percentages of i.v. dose recovered from the GI tract at 24 h as M1 (0.0532% against under the detcction limit), M3 (0.0286% against under the detection limit), and M4 (0.702% against 0.305%*xpressed in terms of DA-125-were significantly greater in the U-ARF rats than in the control rats. All U-ARF rats had ascites, but the concentrations of M1 (0,0320 pgmL-I), M2 (0.0265 pgmL-I), M3 (under the detection limit), and M4 (0.032 pgmL-I) in the ascites from one rat were almost negligible. The plasma concentrations and most of the pharmacokinetic parameters of M1, M2, and M4 were not significantly different between the PCM rats and their control rats.