Efficacy and interactions of oxandrolone, halo-fenate and clofibrate in a factorial study on experimental acute nephrotic hyperlipidemia

J Pharmacol Exp Ther. 1975 Jul;194(1):274-84.

Abstract

Nephrotic mixed hyperlipidemia may be associated with accelerated coronary artery disease. To investigate the response of experimental nephrotic hyperlipidemia to therapy, a 2(4) factorial study of sodium clofibrate and beta-benzalbutyrate, halofenate and oxandrolone (250, 150, 100 and 10 mg/kg/day, respectively) was carried out. Nephrotic syndrome was induced by a single i.p. injection of puromycin aminonucleoside (90 mg/kg) in 80 female white rats of average weight 160 g. Oxandrolone proved to be significantly hypotriglyceridemic in combined therapy (average fall, 38%; P less than .05), and also lowered serum total cholesterol and phospholipid concentrations (23% and 21% falls, P less than .01) and less than .05), due largely to synergistic interactions with clofibrate-like drugs. Hypocholesteremic effects (23 and 22% average falls) were also significant for halofenate (P less than .01) and clofibrate (P less than .05) . Serum triglyceride levels actually rose significantly (P less than .05) with drug combinations containing beta-benzalbutyrate. Clofibrate and its analogs (halofenate and beta-benzalbutyrate) produced significant hepatomegaly (mean responses of +18, +18 and +10%, respectively) whereas oxandrolone produced significant hepatic shrinkage (-10%)(P less than .05). Secondary effects (drug interactions) were also found; hypotriglyceridemic synergism (effects more than additive) occurred between oxandrolone and clofibrate or its analogs (P less than .05), whereas antagonism (effects less than additive) was observed within the clofibrate-like group (P less than .01 or less .05).

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Butyrates / therapeutic use*
  • Cholesterol / blood
  • Clofibrate / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • Glycolates / therapeutic use*
  • Halofenate / therapeutic use*
  • Hyperlipidemias / blood
  • Hyperlipidemias / chemically induced
  • Hyperlipidemias / drug therapy*
  • Lipids / blood
  • Liver / anatomy & histology
  • Nephrotic Syndrome / blood
  • Nephrotic Syndrome / chemically induced
  • Nephrotic Syndrome / drug therapy*
  • Organ Size / drug effects
  • Oxandrolone / therapeutic use*
  • Puromycin Aminonucleoside
  • Rats
  • Statistics as Topic

Substances

  • Butyrates
  • Glycolates
  • Lipids
  • Puromycin Aminonucleoside
  • Oxandrolone
  • Cholesterol
  • Clofibrate
  • Halofenate