DISCOVERY OF NOVEL MICRO-RNGS AND ENDOGENOUS METABOLISED WHICH PREDICT DRUG METABOLISING ENZYME ACTIVITY (CYTOCHROME P450 AND UDP-GLUCURONOSYL TRANSFERASE) IN HUMAN SUBJECTS

Abstract

This study aims to identify non-invasive biomarkers from the plasma and urine which can predict the total midazolam clearance and apparent oral raltegravir clearance in human, to avoid the labour-intensive and time-consuming multiple blood sampling to measure the plasma midazolam and raltegravir concentration in the subjects to determine the systemic clearance of the two drugs. The biomarkers consisted of pre-dose serum miRNAs, plasma metabolites and urine metabolites from 47 healthy volunteers.The sum of 6 cell-free miRNA expression profiles (hsa-miR-30a-5p, hsa-miR-10b-5p, hsa-miR-4257, hsa-miR-33a-5p, hsa-miR-26b-3p and hsa-miR-216a-5p), the urinary 6-hydroxycortisol ratio and plasma 4b-hydroxycholesterol concentration, expressed as a linear regression equation can predict the total midazolam clearance with r=0.73, p<0.001. No suitable biomarkers were found for prediction of apparent oral raltegravir clearance. This finding can be further validated in a prospective trial with a larger sample size.