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Antimicrobial Agents and Chemotherapy, January 1999, p. 96-99, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Effect of Probenecid on the Renal Excretion Mechanism of a New Carbapenem, DA-1131, in Rats and Rabbits

So H. Kim,1 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 Laboratory, Dong-A Pharmaceutical Company, Ltd., 47 Sanggal-Ri, Kiheung-Up, Yongin-Si, Kyunggi-Do 449-900,2 Korea

Received 15 December 1997/Accepted 1 September 1998

The effects of probenecid, an anion transport inhibitor, on the renal excretion mechanism of a new anionic carbapenem, DA-1131, were investigated after a 1-min intravenous infusion of DA-1131 at 100 mg/kg of body weight to rabbits and 50 mg/kg to rats with or without probenecid at 50 mg/kg for both species. In control rabbits, the renal clearance (CLR) of DA-1131 and the glomerular filtration rate based on creatinine clearance (CLCR) were 6.14 ± 2.09 and 2.26 ± 0.589 ml/min/kg, respectively. When considering the less than 10% plasma protein binding of DA-1131 in rabbits, renal tubular secretion of DA-1131 was observed in rabbits. The CLR of DA-1131 (3.87 ± 0.543 ml/min/kg) decreased significantly with treatment with probenecid in rabbits, indicating that the renal tubular secretion of DA-1131 was inhibited by probenecid. However, in control rats, the CLR of DA-1131 (5.80 ± 1.94 ml/min/kg) was comparable to the CLCR (4.29 ± 1.64 ml/min/kg), indicating that DA-1131 was mainly excreted by glomerular filtration in rats. Therefore, it could be expected that the CLR of DA-1131 could not be affected by treatment with probenecid in rats; this was proved by a similar CLR of DA-1131 with treatment with (6.93 ± 0.675 ml/min/kg) or without (5.80 ± 1.94 ml/min/kg) probenecid. Therefore, the renal secretion of DA-1131 is a factor in rabbits but is not a factor in rats.

* Corresponding author. Mailing address: College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Korea. Phone: 822-880-7855 or 822-880-7877. Fax: 822-889-8693. E-mail: leemg{at}plaza.snu.ac.kr.

Antimicrobial Agents and Chemotherapy, January 1999, p. 96-99, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Park, S. W., We, J. S., Kim, G. W., Choi, S. H., Park, H. S. (2002). Stability of New Carbapenem DA-1131 to Renal Dipeptidase (Dehydropeptidase I). Antimicrob. Agents Chemother. 46: 575-577 [Abstract] [Full Text]  
  • Kim, S. H., Kwon, J. W., Kim, W. B., Lee, M. G. (1999). Effects of Cilastatin on the Pharmacokinetics of a New Carbapenem, DA-1131, in Rats, Rabbits, and Dogs. Antimicrob. Agents Chemother. 43: 2524-2527 [Abstract] [Full Text]  
  • Kim, S. H., Kim, W. B., Lee, M. G. (1999). Pharmacokinetic Changes of a New Carbapenem, , after Intravenous Administration to Spontaneously Hypertensive Rats and Deoxycorticosterone Acetate-Salt-Induced Hypertensive Rats. Drug Metab. Dispos. 27: 710-716 [Abstract] [Full Text]  


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