Organ Impairment-Drug-Drug Interaction Database: A Tool for Evaluating the Impact of Renal or Hepatic Impairment and Pharmacologic Inhibition on the Systemic Exposure of Drugs

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? (sic) The effect of DDI, RI, and HI are evaluated during drug development. However, there is a lack of a common database that summarizes results of these studies for the same drug that may help to determine if results from DDI or HI or RI studies can be used to inform the likely impact of other factors if such studies were not conducted. Data from publicly available articles and new drug applications usually present either OI data or drug interaction pharmacokinetic studies. center dot WHAT QUESTION DID THE STUDY ADDRESS? (sic) This database is the first dataset of quantitative data from organ impairment studies presented with the maximum change in drug exposure from a drug-drug inhibition study. center dot WHAT THIS STUDY ADDS TO OUR KNOWLEDGE (sic) For drugs that are highly cleared via CYP3A4, a well-conducted pharmacologic inhibition study may reflect the worst-case scenario for changes in AUC in patients with severe HI. For drugs that are renally eliminated, pharmacologic inhibition with transporter inhibitors does not reflect the worst-case scenario for changes in AUC in severe RI patients, but accurate estimation of the contribution of renal clearance can be useful in predicting a worst-case scenario. center dot HOW THIS MIGHT CHANGE CLINICAL PHARMACOLOGY AND THERAPEUTICS (sic) Public availability of this database will encourage additional analysis and assist development of regulatory recommendations for the evaluation of drug exposure in specific populations by leveraging information from DDI studies.