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Chemical Compound Review

CIL     (Z)-2-[[(1S)-2,2- dimethylcyclopropyl]carbo...

Synonyms: AC1L9JKX
 
 
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Disease relevance of Cilastatin

 

High impact information on Cilastatin

  • Most of the drug is eliminated in the urine, where it is metabolized by an enzyme on the brush border of the renal tubular cells; cilastatin is given simultaneously to inhibit this inactivation [6].
  • As a result, we were able to estimate an average chromosome Y tetranucleotide mutation frequency of 0.20% (95% CIL 0.05-0.55) [7].
  • Expanding the set of microsatellites with two more loci (a tri- and a penta-nucleotide repeat locus) an average chromosome Y microsatellite mutation frequency of 0.21% (95% CIL 0.06-0.49) was found [7].
  • The beta-lactamase inhibitor, cilastatin, demonstrated reversible competitive inhibition of the peptidase-catalyzed hydrolysis of both antibiotics with the same Ki of 0.7 microM [8].
  • There were substantially more gram-negative organisms recovered from the patients with treatment failure who were initially treated with imipenem/cilastatin [9].
 

Chemical compound and disease context of Cilastatin

 

Biological context of Cilastatin

 

Anatomical context of Cilastatin

 

Associations of Cilastatin with other chemical compounds

 

Gene context of Cilastatin

 

Analytical, diagnostic and therapeutic context of Cilastatin

  • The plasma concentration of cilastatin increased with each dose until the next hemodialysis session [32].
  • After intravenous infusion, the nonrenal clearance (CL(NR)) of DA-1131 was significantly slower in rats (3.00 versus 8.01 ml/min/kg) and rabbits (2.41 versus 6.77 ml/min/kg) when the drug was coadministered with cilastatin; this could be due to the slower metabolism of DA-1131 by rat and rabbit kidney DHP-I [33].
  • Plasma levels of cilastatin determined by high-pressure liquid chromatography and radiometry were virtually identical [22].
  • Total clearances of imipenem and cilastatin (mean +/- standard deviations) were 122.2 +/- 28.6 and 29.2 +/- 13.7 ml/min, respectively, with hemofiltration clearances of 22.9 +/- 2.5 and 16.1 +/- 3.1 ml/min, respectively, and nonrenal, nonhemofiltration clearances of 90.8 +/- 26.3 and 13.2 +/- 13.9 ml/min, respectively [34].
  • CONCLUSIONS: Our findings support the hypothesis that cilastatin administration can reduce CsA-induced acute nephrotoxicity after kidney transplantation [23].

References

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  3. Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: experience with imipenem/cilastatin. Calandra, G., Lydick, E., Carrigan, J., Weiss, L., Guess, H. Am. J. Med. (1988) [Pubmed]
  4. Imipenem/cilastatin in the treatment of osteomyelitis. MacGregor, R.R., Gentry, L.O. Am. J. Med. (1985) [Pubmed]
  5. The renal mitochondrial toxicity of beta-lactam antibiotics: in vitro effects of cephaloglycin and imipenem. Tune, B.M., Hsu, C.Y. J. Am. Soc. Nephrol. (1990) [Pubmed]
  6. Imipenem: first of a new class of beta-lactam antibiotics. Barza, M. Ann. Intern. Med. (1985) [Pubmed]
  7. Estimating Y chromosome specific microsatellite mutation frequencies using deep rooting pedigrees. Heyer, E., Puymirat, J., Dieltjes, P., Bakker, E., de Knijff, P. Hum. Mol. Genet. (1997) [Pubmed]
  8. Beta-lactamase activity of purified and partially characterized human renal dipeptidase. Campbell, B.J., Forrester, L.J., Zahler, W.L., Burks, M. J. Biol. Chem. (1984) [Pubmed]
  9. Results of a clinical trial of clinafloxacin versus imipenem/cilastatin for intraabdominal infections. Solomkin, J.S., Wilson, S.E., Christou, N.V., Rotstein, O.D., Dellinger, E.P., Bennion, R.S., Pak, R., Tack, K. Ann. Surg. (2001) [Pubmed]
  10. Acute necrotizing pancreatitis: treatment strategy according to the status of infection. Büchler, M.W., Gloor, B., Müller, C.A., Friess, H., Seiler, C.A., Uhl, W. Ann. Surg. (2000) [Pubmed]
  11. In vitro susceptibility and in vivo efficacy of antimicrobials in the treatment of Bacteroides fragilis-Escherichia coli infection in mice. Brook, I. J. Infect. Dis. (1989) [Pubmed]
  12. Intravenous meropenem versus imipenem/cilastatin in the treatment of serious bacterial infections in hospitalized patients. Meropenem Serious Infection Study Group. Colardyn, F., Faulkner, K.L. J. Antimicrob. Chemother. (1996) [Pubmed]
  13. A randomized multicenter trial of piperacillin/tazobactam versus imipenem/cilastatin in the treatment of severe intra-abdominal infections. Swedish Study Group. Eklund, A.E., Nord, C.E. J. Antimicrob. Chemother. (1993) [Pubmed]
  14. Monotherapy in serious hospital-acquired infections: a clinical trial of ceftazidime versus imipenem/cilastatin. European Study Group. Norrby, S.R., Finch, R.G., Glauser, M. J. Antimicrob. Chemother. (1993) [Pubmed]
  15. Imipenem/cilastatin: pharmacokinetic profile in renal insufficiency. Gibson, T.P., Demetriades, J.L., Bland, J.A. Am. J. Med. (1985) [Pubmed]
  16. Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis. Nitanai, Y., Satow, Y., Adachi, H., Tsujimoto, M. J. Mol. Biol. (2002) [Pubmed]
  17. Nephrotoxicity of vancomycin and drug interaction study with cilastatin in rabbits. Toyoguchi, T., Takahashi, S., Hosoya, J., Nakagawa, Y., Watanabe, H. Antimicrob. Agents Chemother. (1997) [Pubmed]
  18. Safety and efficacy of imipenem/cilastatin in treatment of complicated urinary tract infections. Cox, C.E., Corrado, M.L. Am. J. Med. (1985) [Pubmed]
  19. Identification of membrane dipeptidase as a major glycosyl-phosphatidylinositol-anchored protein of the pancreatic zymogen granule membrane, and evidence for its release by phospholipase A. Hooper, N.M., Cook, S., Lainé, J., Lebel, D. Biochem. J. (1997) [Pubmed]
  20. Insulin stimulates the release of the glycosyl phosphatidylinositol-anchored membrane dipeptidase from 3T3-L1 adipocytes through the action of a phospholipase C. Movahedi, S., Hooper, N.M. Biochem. J. (1997) [Pubmed]
  21. Imipenem pharmacokinetics and body fluid concentrations in patients receiving high-dose treatment for serious infections. MacGregor, R.R., Gibson, G.A., Bland, J.A. Antimicrob. Agents Chemother. (1986) [Pubmed]
  22. Disposition of radiolabeled imipenem and cilastatin in normal human volunteers. Norrby, S.R., Rogers, J.D., Ferber, F., Jones, K.H., Zacchei, A.G., Weidner, L.L., Demetriades, J.L., Gravallese, D.A., Hsieh, J.Y. Antimicrob. Agents Chemother. (1984) [Pubmed]
  23. Effect of cilastatin on cyclosporine-induced acute nephrotoxicity in kidney transplant recipients. Carmellini, M., Frosini, F., Filipponi, F., Boggi, U., Mosca, F. Transplantation (1997) [Pubmed]
  24. Imipenem coadministered with cilastatin compared with moxalactam: integration of serum pharmacokinetics and microbiologic activity following single-dose administration to normal volunteers. Standiford, H.C., Drusano, G.L., Bustamante, C.I., Rivera, G., Forrest, A., Tatem, B., Leslie, J., Moody, M. Antimicrob. Agents Chemother. (1986) [Pubmed]
  25. Identification by site-directed mutagenesis of three essential histidine residues in membrane dipeptidase, a novel mammalian zinc peptidase. Keynan, S., Hooper, N.M., Turner, A.J. Biochem. J. (1997) [Pubmed]
  26. Meropenem versus imipenem/cilastatin in the treatment of intra-abdominal infections. Brismar, B., Malmborg, A.S., Tunevall, G., Lindgren, V., Bergman, L., Mentzing, L.O., Nyström, P.O., Anséhn, S., Bäckstrand, B., Skau, T. J. Antimicrob. Chemother. (1995) [Pubmed]
  27. Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors. Enomoto, A., Takeda, M., Shimoda, M., Narikawa, S., Kobayashi, Y., Kobayashi, Y., Yamamoto, T., Sekine, T., Cha, S.H., Niwa, T., Endou, H. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  28. Treatment of acute bacterial exacerbations of chronic obstructive pulmonary disease in hospitalised patients--a comparison of meropenem and imipenem/cilastatin. COPD Study Group. Hamacher, J., Vogel, F., Lichey, J., Kohl, F.V., Diwok, K., Wendel, H., Lode, H. J. Antimicrob. Chemother. (1995) [Pubmed]
  29. Pharmacokinetic profile of imipenem/cilastatin in normal volunteers. Drusano, G.L., Standiford, H.C. Am. J. Med. (1985) [Pubmed]
  30. The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterial metallo-beta-lactamase enzyme CphA. Keynan, S., Hooper, N.M., Felici, A., Amicosante, G., Turner, A.J. Antimicrob. Agents Chemother. (1995) [Pubmed]
  31. Pharmacokinetics of imipenem-cilastatin in neonates. Freij, B.J., McCracken, G.H., Olsen, K.D., Threlkeld, N. Antimicrob. Agents Chemother. (1985) [Pubmed]
  32. Multiple-dose study of imipenem/cilastatin in patients with end-stage renal disease undergoing long-term hemodialysis. Berman, S.J., Sugihara, J.G., Nakamura, J.M., Kawahara, K.K., Wong, E.G., Musgrave, J.E., Wong, L.M., Siemsen, A.M. Am. J. Med. (1985) [Pubmed]
  33. Effects of cilastatin on the pharmacokinetics of a new carbapenem, DA-1131, in rats, rabbits, and dogs. Kim, S.H., Kwon, J.W., Kim, W.B., Lee, M.G. Antimicrob. Agents Chemother. (1999) [Pubmed]
  34. Pharmacokinetics of imipenem-cilastatin in critically ill patients undergoing continuous venovenous hemofiltration. Tegeder, I., Bremer, F., Oelkers, R., Schobel, H., Schüttler, J., Brune, K., Geisslinger, G. Antimicrob. Agents Chemother. (1997) [Pubmed]
 
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