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Updated: Jan 23, 2026
Direct Drug Delivery to Kidney via the Renal Artery
Published on: April 17, 2021
Predicting the Need for a Tier II Ototoxicity Study From Early Renal Function Data
David V Gauvin1, Zachary J Zimmermann1, Joshua Yoder1
11 Neurobehavioral Sciences Department, Charles River Laboratories, Inc, Mattawan, MI, USA.
Abstract:
History has established that many drugs, such as the antibiotics, chemotherapies, and loop diuretics, are capable of inducing both nephrotoxicity and ototoxicity. The exact mechanisms by which cellular damage occurs remain to be fully elucidated. Monitoring the indices of renal function conducted in the Food and Drug Administration's prescribed set of early investigational new drug (IND)-enabling studies may be the first signs of ototoxicity properties of the new drug candidate. In developing improved and efficacious new molecular entities, it is critically necessary to understand the cellular and molecular mechanisms underlying the potential ototoxic effects as early in the drug development program as possible. Elucidation of these mechanisms will facilitate the development of safe and effective clinical approaches for the prevention and amelioration of drug-induced ototoxicity prior to the first dose in man. Biomarkers for nephrotoxicity in early tier I or tier II nonclinical IND-enabling studies should raise an inquiry as to the need to conduct a full auditory function assay early in the game to clear the pipeline with a safer candidate that has a higher probability of continued therapeutic compliance once approved for distribution.
Insights
Early detection of drug-induced ototoxicity is crucial. Monitoring kidney function in early drug development studies may signal potential hearing damage, enabling safer drug candidates.
Area of Science:
- Pharmacology
- Toxicology
- Drug Development
Background:
- Many drugs, including antibiotics and chemotherapies, can cause kidney (nephrotoxicity) and ear (ototoxicity) damage.
- The precise mechanisms of this cellular damage are not fully understood.
- Early detection of potential ototoxicity is vital for developing safer medications.
Purpose of the Study:
- To emphasize the importance of early identification of drug-induced ototoxicity during drug development.
- To highlight the need for understanding the cellular and molecular mechanisms of ototoxicity.
- To propose using kidney function biomarkers as an early indicator for auditory function testing.
Main Methods:
- Review of historical drug-induced toxicities.
- Analysis of standard early investigational new drug (IND)-enabling studies.
- Correlation of renal function monitoring with potential ototoxic effects.
Main Results:
- Kidney function indices in early studies may serve as preliminary indicators of ototoxicity.
- Understanding molecular mechanisms is key to preventing ototoxicity.
- Early auditory function assays can help identify safer drug candidates.
Conclusions:
- Integrating ototoxicity assessments early in drug development is essential.
- Biomarkers for nephrotoxicity should prompt investigation into ototoxic potential.
- This approach can lead to safer drugs with better patient compliance.
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