Abstract | OBJECTIVES: 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.
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Authors | Seung Yon Han, Si Hyung Yang, Insoo Yoon, Myung Gull Lee, Young Hee Choi |
Journal | The Journal of pharmacy and pharmacology
(J Pharm Pharmacol)
Vol. 64
Issue 10
Pg. 1452-60
(Oct 2012)
ISSN: 2042-7158 [Electronic] England |
PMID | 22943176
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society. |
Chemical References |
- Aminocaproates
- Organic Anion Transporters
- Uranyl Nitrate
- 6-acetylaminocaproic acid
- Aminocaproic Acid
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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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