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Antimicrobial Agents and Chemotherapy, May 1998, p. 1217-1221, Vol. 42, No. 5
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Pharmacokinetics of a New Carbapenem, DA-1131, after Intravenous Administration to Rats with Uranyl Nitrate-Induced Acute Renal Failure

So H. Kim,1 Hyun J. Shim,2 Won B. Kim,2 and Myung G. Lee1,*

College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742,1 and Research Laboratories, Dong-A Pharmaceutical Company, Ltd., 47 Sanggal-Ri, Kiheung-Up, Yongin-Gun, Kyunggi-Do 449-900,2 Korea

Received 21 May 1997/Returned for modification 31 December 1997/Accepted 23 February 1998

Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of DA-1131, a new carbapenem antibiotic, were investigated after 1-min intravenous administration of the drug (50 mg/kg of body weight) to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF rats). The impaired kidney function was observed in U-ARF rats on the basis of physiological parameters observed by microscopy of the kidney and obtained by chemical analysis of the plasma. After a 1-min intravenous infusion of DA-1131, the concentrations in plasma and the total area under the plasma concentration-time curve from time zero to time infinity increased significantly in U-ARF rats compared with those in control rats (13,000 versus 4,400 µg · min/ml). This was due to the significantly slower total body clearance (CL) of DA-1131 (3.84 versus 11.4 ml/min/kg) from U-ARF rats than from control rats. The significantly slower CL of DA-1131 from U-ARF rats was due to both significantly slower renal clearance (0.000635 versus 4.95 ml/min/kg because of a significant decrease in the 8-h urinary excretion of unchanged DA-1131 [1.54 versus 43.8% of the intravenous dose] due to impaired kidney function, as proved by the significant decrease in creatinine clearance [0.0159 versus 4.29 ml/min/kg]) and significantly slower nonrenal clearance (3.80 versus 6.34 ml/min/kg because of a significant decrease in the metabolism of DA-1131 in the kidney) in U-ARF rats. The amounts of DA-1131 recovered from all tissues studied (except the kidneys) were significantly higher for U-ARF rats than for control rats; however, the ratios of the amount in tissue to the concentration in plasma (except those for the kidney, small intestine, and spleen) were not significantly different between the two groups of rats, indicating that the affinity of DA-1131 for rat tissues was not changed considerably in U-ARF rats.

* Corresponding author. Mailing address: College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Korea. Phone: 82-2-880-7855. Fax: 82-2-889-8693. E-mail: leemg{at}plaza.snu.ac.kr.

Antimicrobial Agents and Chemotherapy, May 1998, p. 1217-1221, Vol. 42, No. 5
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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