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EFFECTS OF CYCLOSPORIN A, GENTAMICIN AND FUROSEMIDE ON RAT RENAL FUNCTION: A LITHIUM CLEARANCE STUDY
Author(s) -
Dieperink Hans,
Leyssac Paul P.,
Starklint Henrik,
Kemp Ejvind
Publication year - 1987
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1987.tb02419.x
Subject(s) - furosemide , renal function , fractional excretion of sodium , gentamicin , renal sodium reabsorption , chemistry , nephrotoxicity , endocrinology , pharmacology , medicine , nephron , reabsorption , lithium (medication) , sodium , kidney , biochemistry , antibiotics , organic chemistry
SUMMARY 1. This study applied clearance methods of inulin, lithium, potassium, sodium and para‐aminohippuric acid (PAH) for investigation of the effects of cyclosporin A (CyA), furosemide and gentamicin on rat ( n = 92) renal function. The drugs were dosed for 2 weeks; CyA 12.5 mg/kg per day, gentamicin 32 mg/kg per day and furosemide 5 mg/kg per day. 2. The questions asked were: could these methods differentiate the effects of drugs with different sites of action, and would gentamicin or furosemide exaggerate the nephrotoxicity of CyA? 3. Furosemide increased sodium clearance (C Na ) 74% and fractional sodium clearance (FENa) 105%, while fractional sodium reabsorption in the distal nephron (FDNR) was reduced, compared with placebo‐treated controls. 4. Gentamicin reduced C PAH 29% and C in 37%, while FE Na increased 335%. Proximal fractional reabsorption (PFR) and absolute proximal reabsorption (APR) decreased. 5. CyA depressed C PAH 32% and lithium clearance (C Li ) 56%, and increased PFR. 6. The effects of CyA and furosemide in reducing renal function were not additive. 7. CyA plus gentamicin reduced C PAH to 35% of the value in untreated controls, equal to 52% of the C PAH of CyA‐treated rats; C in was reduced to 46% of the C in of CyA‐treated rats. 8. Rats given CyA, furosemide and gentamicin had decreased C in , CPAH and C Li compared with rats given either CyA plus furosemide or gentamicin plus furosemide. 9. Thus, in this investigation of drugs known to have different sites of actions, the differences in renal and tubular function were discernible with the lithium clearance method. 10. The nephrotoxicities of CyA and of gentamicin were additive, while furosemide did not aggravate CyA nephrotoxicity.