Effects of Fosfomycin and Imipenem/cilastatin on Nephrotoxicity and Renal Excretion of Vancomycin in Rats

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 1998 Jun 10

PMID 9619782

Citations 11

Authors

T Nakamura

Y Hashimoto

T Kokuryo

K I Inui

Affiliations

Soon will be listed here.

Abstract

Purpose: The effects of fosfomycin and imipenem/cilastatin on the nephrotoxicity of vancomycin were studied in rats, and those on the renal handling of vancomycin were also investigated in perfused kidneys.

Methods: The protective effects of fosfomycin and imipenem/cilastatin on vancomycin nephrotoxicity were evaluated by increases in plasma concentration of creatinine and urea nitrogen in rats. The urinary excretion of vancomycin was measured and analyzed kinetically in the perfused rat kidney.

Results: The nephrotoxicity induced by vancomycin (500 mg/kg, i.v.) was inhibited almost completely by co-administration of fosfomycin or imipenem/cilastatin. In the perfused rat kidney, the excretion ratio of vancomycin was less than those of p-aminohippurate and cimetidine, and greater than that of arbekacin, suggesting the secretion and reabsorption of vancomycin in renal tubules. The tissue/perfusate ratios of unbound vancomycin were not significantly changed by co-treatment with fosfomycin or imipenem/cilastatin. Imipenem/cilastatin significantly decreased the excretion ratio of vancomycin. Fosfomycin also decreased vancomycin excretion ratio, although this effect was not significant.

Conclusions: The renal handling of vancomycin was different from those of organic anions and cations and an aminoglycoside antibiotic. The protective effects of fosfomycin and imipenem/cilastatin against the nephrotoxicity of vancomycin might be partly due to the change in renal handling of vancomycin, probably in its tubular secretion/ reabsorption, in rats.

Citing Articles

Identification of Patients Who Require Two-Point Blood Sampling for the Peak and Trough Values Rather Than One-Point Blood Sampling for the Trough Value for the Evaluation of AUC of Vancomycin Using Bayesian Estimation.

Suzuki A, Samura M, Ishigo T, Fujii S, Ibe Y, Yoshida H Pharm Res. 2024; 41(11):2161-2171.

PMID: 39433691 DOI: 10.1007/s11095-024-03781-4.

Effect of Imipenem, Fosfomycin, Colistin, and Gentamicin Combination against Carbapenem-resistant and Biofilm-forming Isolated from Burn Patients.

Memar M, Adibkia K, Farajnia S, Kafil H, Khalili Y, Azargun R Iran J Pharm Res. 2021; 20(2):286-296.

PMID: 34567162 PMC: 8457740. DOI: 10.22037/ijpr.2020.111824.13380.

Protective effects of lutein against vancomycin-induced acute renal injury in mice via upregulation of peroxisome proliferator-activated receptor gamma/nuclear factor erythroid 2-related factor 2 and inhibition nuclear factor-kappaB/caspase 3.

Emeka P, Rasool S, Morsy M, Islam M, Chohan M Korean J Physiol Pharmacol. 2021; 25(4):321-331.

PMID: 34187949 PMC: 8255119. DOI: 10.4196/kjpp.2021.25.4.321.

Vancomycin-Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention.

Pais G, Liu J, Zepcan S, Avedissian S, Rhodes N, Downes K Pharmacotherapy. 2020; 40(5):438-454.

PMID: 32239518 PMC: 7331087. DOI: 10.1002/phar.2388.

Cilastatin protects against imipenem-induced nephrotoxicity inhibition of renal organic anion transporters (OATs).

Huo X, Meng Q, Wang C, Zhu Y, Liu Z, Ma X Acta Pharm Sin B. 2019; 9(5):986-996.

PMID: 31649848 PMC: 6804466. DOI: 10.1016/j.apsb.2019.02.005.

References

Gruss E, Tomas J, Bernis C, Rodriguez F, Traver J, Fernandez-Ranada J . Nephroprotective effect of cilastatin in allogeneic bone marrow transplantation. Results from a retrospective analysis. Bone Marrow Transplant. 1996; 18(4):761-5. View

Nakamura T, Takano M, Yasuhara M, Inui K . In-vivo clearance study of vancomycin in rats. J Pharm Pharmacol. 1996; 48(11):1197-200. DOI: 10.1111/j.2042-7158.1996.tb03920.x. View

Hori R, He Y, Saito Y, Kamiya A, Tanigawara Y . Moment analysis of drug disposition in kidney. V: In vivo transepithelial transport of p-aminohippurate in rat kidney. J Pharmacokinet Biopharm. 1991; 19(1):51-70. DOI: 10.1007/BF01062192. View

Takano M, Inui K, Okano T, Hori R . Cimetidine transport in rat renal brush border and basolateral membrane vesicles. Life Sci. 1985; 37(17):1579-85. DOI: 10.1016/0024-3205(85)90476-x. View

Marre R, Schulz E, Hedtke D, Sack K . Influence of fosfomycin and tobramycin on vancomycin-induced nephrotoxicity. Infection. 1985; 13(4):190-2. DOI: 10.1007/BF01642811. View

Pritchard J, Miller D . Mechanisms mediating renal secretion of organic anions and cations. Physiol Rev. 1993; 73(4):765-96. DOI: 10.1152/physrev.1993.73.4.765. View

Beauchamp D, Gourde P, Simard M, Bergeron M . Subcellular localization of tobramycin and vancomycin given alone and in combination in proximal tubular cells, determined by immunogold labeling. Antimicrob Agents Chemother. 1992; 36(10):2204-10. PMC: 245477. DOI: 10.1128/AAC.36.10.2204. View

Hall S, Rowland M . Influence of fraction unbound upon the renal clearance of furosemide in the isolated perfused rat kidney. J Pharmacol Exp Ther. 1985; 232(1):263-8. View

Silverblatt F, Kuehn C . Autoradiography of gentamicin uptake by the rat proximal tubule cell. Kidney Int. 1979; 15(4):335-45. DOI: 10.1038/ki.1979.45. View

10.

Hori R, Tanigawara Y, Saito Y, Hayashi Y, Aiba T, Okumura K . Moment analysis of drug disposition in kidney: transcellular transport kinetics of p-aminohippurate in the isolated perfused rat kidney. J Pharm Sci. 1988; 77(6):471-6. DOI: 10.1002/jps.2600770602. View

11.

Toyoguchi T, Nakagawa Y . [Nephrotoxicity and drug interaction of vancomycin (2)]. Nihon Yakurigaku Zasshi. 1996; 107(5):225-35. DOI: 10.1254/fpj.107.225. View

12.

Saito M, Masaki T, Kato H, Numasaka K . [A clinical evaluation of the protective effect of fosfomycin (FOM) against the cis-diamminedichloroplatinum (CDDP)-induced nephrotoxicity]. Hinyokika Kiyo. 1988; 34(5):782-9. View

13.

Cook F, Farrar Jr W . Vancomycin revisited. Ann Intern Med. 1978; 88(6):813-8. DOI: 10.7326/0003-4819-88-6-813. View

14.

Leader W, CHANDLER M, Castiglia M . Pharmacokinetic optimisation of vancomycin therapy. Clin Pharmacokinet. 1995; 28(4):327-42. DOI: 10.2165/00003088-199528040-00005. View

15.

Kumon H, Mizuno A, Nasu Y, Tsugawa M, Kishi M, Ohmori H . [Pharmacokinetics of arbekacin in healthy volunteers and patients with renal insufficiency]. Jpn J Antibiot. 1989; 42(1):200-7. View

16.

Collier V, Lietman P, Mitch W . Evidence for luminal uptake of gentamicin in the perfused rat kidney. J Pharmacol Exp Ther. 1979; 210(2):247-51. View

17.

Wedeen R, Batuman V, Cheeks C, Marquet E, Sobel H . Transport of gentamicin in rat proximal tubule. Lab Invest. 1983; 48(2):212-23. View

18.

Nakamura T, Kokuryo T, Takano M, Inui K . Renal excretion of vancomycin in rats with acute renal failure. J Pharm Pharmacol. 1997; 49(2):154-7. DOI: 10.1111/j.2042-7158.1997.tb06771.x. View