The isolated perfused rat kidney model: a useful tool for drug discovery and development.
Over the past three decades, the Isolated Perfused Rat Kidney (IPK) has been used to study numerous aspects of renal drug disposition. Among the available ex-vivo methods to study renal transport, the IPK allows for elucidation of the overall contributions of renal transport mechanisms on drug excretion. Therefore, IPK studies can provide a bridge between in vitro findings and in vivo disposition. This review paper begins with a detailed overview of IPK methodology (system components, surgical procedure, study design). Various applications of the IPK are then presented. These applications include characterizing renal excretion mechanisms, screening for clinically significant drug interactions, studying renal drug metabolism, and correlating renal drug disposition with drug-induced changes in kidney function. Lastly, the role of IPK studies in drug development is discussed. Demonstrated correlations between IPK data and clinical outcomes make the IPK model a potentially useful tool for drug discovery and evaluation.
Taft
David R
DR
Division of Pharmaceutics and Industrial Pharmacy, Long Island University, 75 DeKalb Avenue, Brooklyn, NY 11201, USA. dtaft@liu.edu
D000465:Algorithms; D000818:Animals; D002021:Buffers; D003627:Data Interpretation, Statistical; D015195:Drug Design; D004347:Drug Interactions; D004395:Dye Dilution Technique; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000502:physiology* / Q000601:surgery; D008954:Models, Biological; D010477:Perfusion; D004364:Pharmaceutical Preparations / Q000378:metabolism / Q000652:urine; D010599:Pharmacokinetics; D011485:Protein Binding; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology
D002021:Buffers; D004364:Pharmaceutical Preparations