About this Journal Submit a Manuscript Table of Contents
Advances in Pharmacological Sciences
Volume 2011 (2011), Article ID 204501, 7 pages
http://dx.doi.org/10.1155/2011/204501
Research Article

Pharmacokinetics of p-Aminohippuric Acid and Inulin in Rabbits with Aristolochic Acid Nephropathy

College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11014, Taiwan

Received 30 October 2010; Revised 14 January 2011; Accepted 1 March 2011

Academic Editor: Masahiro Oike

Copyright © 2011 Chiao-Shih Tseng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The characteristics of aristolochic acid nephropathy (AAN) are interstitial fibrosis and atrophy of the proximal tubules, but with no change in glomeruli. To investigate the effects of AA on renal functions and the pharmacokinetics (PKs) of p-aminohippuric acid (PAH) and inulin, New Zealand white rabbits were used in this study. The plasma concentrations of PAH and inulin were determined by validated HPLC methods. After a single intravenous administration of 0.5 mg/kg aristolochic acid sodium (AANa), rabbits exhibited mild to moderate nephrotoxicity on the 7th day. Significant tubulointerstitial damage to kidney specimens was found, but there were no remarkable glomerular changes. Clearance rates of PAH and inulin both significantly decreased in AANa-treated rabbits. In addition, there was a significant correlation among the degree of tubulointerstitial changes and PK parameters of PAH after AANa administration, but no correlation was noted with the PKs of inulin. With mild to moderate AAN in rabbits, the renal plasma flow significantly decreased by 55%, and the glomerular filtration rate also significantly decreased by 85%. In conclusion, major renal lesions were found on proximal tubules after AANa administration. The PKs of PAH and inulin significantly changed, and kidney functions, including the RPF and GFR, were reduced.