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

Han, Seung Yon; Yang, Si Hyung; Yoon, Insoo; Lee, Myung Gull; Choi, Young Hee

Objectives 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 ( Clr and Clnr, respectively) compared with control rats. Slower Clnr was partly due to a decrease in the metabolism in liver and/or intestine. Slower Clr 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.

LABORATORY rats; ACUTE kidney failure; URANYL compounds; NITRATES; METABOLISM

Journal of Pharmacy & Pharmacology, 2012, Vol 64, Issue 10, p1452

0022-3573

Academic Journal

10.1111/j.2042-7158.2012.01517.x