Effect of phenobarbital and cimetidine on experimental cyclosporine nephrotoxicity

Preliminary observations

D. E. Schwass, A. W. Sasaki, Donald Houghton, K. E. Benner, W. M. Bennett

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Cyclosporine is metabolized by the hepatic microsomal cytochrome P-450 mixed function oxidases. To determine the effects of inducers and inhibitors of this enzyme on nephrotoxicity, male Fischer 344 rats were treated with cyclosporine in doses of 25 mg/kg and 40 mg/kg by daily gavage for 14 days. Groups of animals were given phenobarbital 75 mg/kg i.p., cimetidine 75 mg/kg i.p., or .9% saline i.p. for 3 days prior to starting cyclosporine and throughout therapy. Animals treated with the oil vehicle for cyclosporine served as controls. Animals receiving cyclosporine together with phenobarbital had better preservation of glomerular filtration rate than did other cyclosporine-treated animals. Cimetidine did not enhance cyclosporine nephrotoxicity. Direct tubular toxicity was not evident using cortical slice transport of tetraethylammonium, fractional excretion of sodium and light microscopy as markers. If phenobarbital protects from cyclosporine nephrotoxicity because of its enzyme inducing action, it would follow that the parent drug and not a toxic metabolite mediated renal dysfunction. Based on the decreased glomerular filtration rate in the absence of overt tubular damage the major mechanism of cyclosporine nephrotoxicity is probably related to vascular or glomerular effects of the drug.

Original languageEnglish (US)
JournalClinical Nephrology
Volume25
Issue numberSUPPL. 1
StatePublished - 1986

Fingerprint

Cimetidine
Phenobarbital
Cyclosporine
Glomerular Filtration Rate
Tetraethylammonium
Poisons
Inbred F344 Rats
Enzyme Inhibitors
Mixed Function Oxygenases
Pharmaceutical Preparations
Cytochrome P-450 Enzyme System
Blood Vessels
Microscopy
Oils
Sodium
Kidney
Light
Liver
Enzymes

ASJC Scopus subject areas

  • Nephrology

Cite this

Effect of phenobarbital and cimetidine on experimental cyclosporine nephrotoxicity : Preliminary observations. / Schwass, D. E.; Sasaki, A. W.; Houghton, Donald; Benner, K. E.; Bennett, W. M.

In: Clinical Nephrology, Vol. 25, No. SUPPL. 1, 1986.

Research output: Contribution to journalArticle

Schwass, D. E. ; Sasaki, A. W. ; Houghton, Donald ; Benner, K. E. ; Bennett, W. M. / Effect of phenobarbital and cimetidine on experimental cyclosporine nephrotoxicity : Preliminary observations. In: Clinical Nephrology. 1986 ; Vol. 25, No. SUPPL. 1.
@article{306739e699394272bb4f68b38f684de4,
title = "Effect of phenobarbital and cimetidine on experimental cyclosporine nephrotoxicity: Preliminary observations",
abstract = "Cyclosporine is metabolized by the hepatic microsomal cytochrome P-450 mixed function oxidases. To determine the effects of inducers and inhibitors of this enzyme on nephrotoxicity, male Fischer 344 rats were treated with cyclosporine in doses of 25 mg/kg and 40 mg/kg by daily gavage for 14 days. Groups of animals were given phenobarbital 75 mg/kg i.p., cimetidine 75 mg/kg i.p., or .9{\%} saline i.p. for 3 days prior to starting cyclosporine and throughout therapy. Animals treated with the oil vehicle for cyclosporine served as controls. Animals receiving cyclosporine together with phenobarbital had better preservation of glomerular filtration rate than did other cyclosporine-treated animals. Cimetidine did not enhance cyclosporine nephrotoxicity. Direct tubular toxicity was not evident using cortical slice transport of tetraethylammonium, fractional excretion of sodium and light microscopy as markers. If phenobarbital protects from cyclosporine nephrotoxicity because of its enzyme inducing action, it would follow that the parent drug and not a toxic metabolite mediated renal dysfunction. Based on the decreased glomerular filtration rate in the absence of overt tubular damage the major mechanism of cyclosporine nephrotoxicity is probably related to vascular or glomerular effects of the drug.",
author = "Schwass, {D. E.} and Sasaki, {A. W.} and Donald Houghton and Benner, {K. E.} and Bennett, {W. M.}",
year = "1986",
language = "English (US)",
volume = "25",
journal = "Clinical Nephrology",
issn = "0301-0430",
publisher = "Dustri-Verlag Dr. Karl Feistle",
number = "SUPPL. 1",

}

TY - JOUR

T1 - Effect of phenobarbital and cimetidine on experimental cyclosporine nephrotoxicity

T2 - Preliminary observations

AU - Schwass, D. E.

AU - Sasaki, A. W.

AU - Houghton, Donald

AU - Benner, K. E.

AU - Bennett, W. M.

PY - 1986

Y1 - 1986

N2 - Cyclosporine is metabolized by the hepatic microsomal cytochrome P-450 mixed function oxidases. To determine the effects of inducers and inhibitors of this enzyme on nephrotoxicity, male Fischer 344 rats were treated with cyclosporine in doses of 25 mg/kg and 40 mg/kg by daily gavage for 14 days. Groups of animals were given phenobarbital 75 mg/kg i.p., cimetidine 75 mg/kg i.p., or .9% saline i.p. for 3 days prior to starting cyclosporine and throughout therapy. Animals treated with the oil vehicle for cyclosporine served as controls. Animals receiving cyclosporine together with phenobarbital had better preservation of glomerular filtration rate than did other cyclosporine-treated animals. Cimetidine did not enhance cyclosporine nephrotoxicity. Direct tubular toxicity was not evident using cortical slice transport of tetraethylammonium, fractional excretion of sodium and light microscopy as markers. If phenobarbital protects from cyclosporine nephrotoxicity because of its enzyme inducing action, it would follow that the parent drug and not a toxic metabolite mediated renal dysfunction. Based on the decreased glomerular filtration rate in the absence of overt tubular damage the major mechanism of cyclosporine nephrotoxicity is probably related to vascular or glomerular effects of the drug.

AB - Cyclosporine is metabolized by the hepatic microsomal cytochrome P-450 mixed function oxidases. To determine the effects of inducers and inhibitors of this enzyme on nephrotoxicity, male Fischer 344 rats were treated with cyclosporine in doses of 25 mg/kg and 40 mg/kg by daily gavage for 14 days. Groups of animals were given phenobarbital 75 mg/kg i.p., cimetidine 75 mg/kg i.p., or .9% saline i.p. for 3 days prior to starting cyclosporine and throughout therapy. Animals treated with the oil vehicle for cyclosporine served as controls. Animals receiving cyclosporine together with phenobarbital had better preservation of glomerular filtration rate than did other cyclosporine-treated animals. Cimetidine did not enhance cyclosporine nephrotoxicity. Direct tubular toxicity was not evident using cortical slice transport of tetraethylammonium, fractional excretion of sodium and light microscopy as markers. If phenobarbital protects from cyclosporine nephrotoxicity because of its enzyme inducing action, it would follow that the parent drug and not a toxic metabolite mediated renal dysfunction. Based on the decreased glomerular filtration rate in the absence of overt tubular damage the major mechanism of cyclosporine nephrotoxicity is probably related to vascular or glomerular effects of the drug.

UR - http://www.scopus.com/inward/record.url?scp=0022642140&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022642140&partnerID=8YFLogxK

M3 - Article

VL - 25

JO - Clinical Nephrology

JF - Clinical Nephrology

SN - 0301-0430

IS - SUPPL. 1

ER -