A guidance for renal biomarker lead optimization and use in translational pharmacodynamics

Drug Discov Today. 2010 Feb;15(3-4):142-7. doi: 10.1016/j.drudis.2009.12.001. Epub 2009 Dec 21.

Abstract

Guidance for the use of biomarkers in pharmaceutical development and clinical trial optimization will reduce developmental cycle time. A 'fit-for-purpose' guidance for biomarker use is considered herein when the same biomarker is applied in very different contexts in drug development and after regulatory approval. Recent approved use of renal safety biomarkers in Good Laboratory Practice studies lacks sufficient guidance for the use of these markers across the drug development pipeline. In lead optimization, renal injury biomarkers are possible anchors for promising new prodromal metabolic biomarkers, which are applied before lead candidate selection. Renal injury biomarkers can now be evaluated as potential efficacy and pharmacodynamic biomarkers in clinical trial proof-of-concept studies for diabetic nephropathy.

Publication types

  • Review

MeSH terms

  • Albumins / metabolism
  • Animals
  • Autoimmune Diseases / metabolism
  • Bile Acids and Salts / metabolism
  • Biomarkers, Pharmacological / metabolism*
  • Cathepsin B / urine
  • Cyclosporine / adverse effects
  • Cystatin C / blood
  • Cysteine / metabolism
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / urine
  • Drug Approval
  • Drug Evaluation, Preclinical / methods*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Kidney / blood supply
  • Kidney / drug effects
  • Kidney / metabolism*
  • Leukotrienes / metabolism
  • Models, Animal
  • Translational Research, Biomedical / methods*

Substances

  • Albumins
  • Bile Acids and Salts
  • Biomarkers, Pharmacological
  • Cystatin C
  • Immunosuppressive Agents
  • Leukotrienes
  • cysteinyl-leukotriene
  • Cyclosporine
  • Cathepsin B
  • Cysteine