ABSTRACT We aimed to construct a linear regression-based model between area-under-curve (AUCr) and the therapeutic range-to-inhibition constant ratio (TR-to-Ki). As result, a linear log-log regression model, between the averaged AUCr, calculated as the mean from the values of different drug-drug interactions (DDIs) between several victim-drugs with the same inhibitor (AUCr avg), and the mean TR-to-Ki ratio (TRm-to-Ki), calculated as the mean value between the maximum and minimum TR of the inhibitor divided by its Ki, obtained the best correlation (r2 = 0.72; p = 0.0116). Accordingly, a drug-drug interaction involving reversible inhibitory drugs of CYP2D6 could be managed by adjusting dose of victim and/or inhibitory drug to the magnitude of the desired change, by applying data of TR and Ki of inhibitor to the equation of regression line presented here.
View Full Article
|