title: Reduced clearance of ε-acetamidocaproic acid in rats with acute renal failure induced by uranyl nitrate.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Seung Yon
authors.initials: SY
authors.lastname: Han
authors.forename: Si Hyung
authors.initials: SH
authors.lastname: Yang
authors.forename: Insoo
authors.initials: I
authors.lastname: Yoon
authors.forename: Myung Gull
authors.initials: MG
authors.lastname: Lee
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Choi
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology*; D000284:Administration, Oral; D000614:Aminocaproates; D015119:Aminocaproic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D027361:Organic Anion Transporters / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014502:Uranyl Nitrate / Q000633:toxicity
chemical_list: D000614:Aminocaproates; D027361:Organic Anion Transporters; D014502:Uranyl Nitrate; C018802:6-acetylaminocaproic acid; D015119:Aminocaproic Acid