Effect of a hepatoprotective agent, YH-439, on the pharmacokinetics of furosemide and azosemide in rats.

The effect of YH-439 pretreatment on the pharmacokinetics of furosemide and azosemide was investigated after intravenous (iv) administration of furosemide, 6 mg per whole body weight, and azosemide, 10 mg per kg body weight, to rats pretreated with 3 consecutive daily oral administration of YH-439, 200 mg per kg body weight. The nonrenal clearance of furosemide (2.20 versus 3.53 ml/min/kg) increased significantly, and the 24 h-urinary excretion of furosemide (both the amount and percentages of iv dose) decreased significantly in the YH-439 treated rats when compared with those in the control rats. The results were unexpected since the metabolism of furosemide increased by pretreatment with phenobarbital (CYP2B inducer) and YH-439 pretreatment failed to affect CYP2B expression. The increased metabolism of furosemide by pretreatment with YH-439 could be due to other enzyme(s) induced by pretreatment with YH-439. Pharmacokinetic parameters of azosemide were not significantly different between the two groups of rats except t(1/2), MRT, and V(ss). The results were unexpected since azosemide metabolism increased with 3-methylchloranthane (3-MC, CYP1A inducer) and YH-439 pretreatment increased CYP1A expression. Above data indicate that the expression of CYP1A by treatment with YH-439 was not considerable when compared with that with 3-MC.
AuthorsS H Kim, K J Park, W H Yoon, J W Lee, N D Kim, M G Lee
JournalResearch communications in molecular pathology and pharmacology (Res Commun Mol Pathol Pharmacol) Vol. 91 Issue 2 Pg. 233-44 (Feb 1996) ISSN: 1078-0297 [Print] UNITED STATES
PMID8832915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Diuretics
  • Sulfanilamides
  • Thiazoles
  • YH 439
  • Furosemide
  • azosemide
  • Animals
  • Area Under Curve
  • Diuretics (administration & dosage, pharmacokinetics)
  • Drug Interactions
  • Drug-Induced Liver Injury (prevention & control)
  • Furosemide (administration & dosage, pharmacokinetics)
  • Half-Life
  • Injections, Intravenous
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sulfanilamides (administration & dosage, pharmacokinetics)
  • Thiazoles (pharmacology)

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