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Reduced clearance of ε-acetamidocaproic acid in rats with acute renal failure induced by uranyl nitrate.

AbstractOBJECTIVES:
Anti-ulcer drugs are frequently used in patients with acute renal failure (ARF). Zinc acexamate is ionized to zinc and ε-acetamidocaproic acid and free EACA exerts a potent therapeutic effect in treating gastric or duodenal ulcers with few side effects. Thus, pharmacokinetic changes in rats with acute renal failure induced by uranyl nitrate (U-ARF rats) were investigated in this study.
METHODS:
The in-vivo pharmacokinetics and in-vitro hepatic/intestinal metabolism of EACA were assessed using control and U-ARF rats. The mechanism of urinary excretion of EACA was further investigated in rats.
KEY FINDINGS:
After intravenous and oral administration of zinc acexamate to U-ARF rats, there were significant increases in the values of the area under the curve (AUC) and decreases in the values for time-averaged renal and nonrenal clearances (Cl(r) and Cl(nr) , respectively) compared with control rats. Slower Cl(nr) was partly due to a decrease in the metabolism in liver and/or intestine. Slower Cl(r) could have been due to urine flow rate-dependent timed-interval renal clearance, decrease in organic anion transporter-mediated renal excretion (drug interaction with probenecid and decrease in the relative contribution of net secretion compared with glomerular filtration in U-ARF rats) and/or impaired kidney function.
CONCLUSIONS:
The pharmacokinetics were significantly altered in U-ARF rats due to the changes in both the hepatic/intestinal metabolism and urinary excretion.
AuthorsSeung Yon Han, Si Hyung Yang, Insoo Yoon, Myung Gull Lee, Young Hee Choi
JournalThe Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 64 Issue 10 Pg. 1452-60 (Oct 2012) ISSN: 2042-7158 [Electronic] England
PMID22943176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.
Chemical References
  • Aminocaproates
  • Organic Anion Transporters
  • Uranyl Nitrate
  • 6-acetylaminocaproic acid
  • Aminocaproic Acid
Topics
  • Acute Kidney Injury (physiopathology)
  • Administration, Oral
  • Aminocaproates
  • Aminocaproic Acid (administration & dosage, pharmacokinetics)
  • Animals
  • Area Under Curve
  • Disease Models, Animal
  • Glomerular Filtration Rate
  • Infusions, Intravenous
  • Intestinal Mucosa (metabolism)
  • Liver (metabolism)
  • Male
  • Organic Anion Transporters (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Uranyl Nitrate (toxicity)

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