The most important cluster of these conditions, has high positive factor loadings for BLCMKT, TDEP, MARME, and REPR, and has negative factor loadings for both PLI and TLI.
Table A1: Factor loadings of the first two principal components of 11 initial conditions and of the first principal component of eight initial conditions Initial Principal Principal Principal condition component 1 component 2 component 1 variables (11 initial (11 initial (8 initial conditions) conditions) conditions) 1 2 3 Y1990 0.234 -0.237 -- STATE -0.359 0.182 -- PRGR 0.240 0.011 -- RICH -0.193 0.438 -- TDEP 0.438 0.111 0.465 BLCMKT 0.402 0.303 0.511 INDIST -0.056 0.384 0.036 URBAN 0.318 0.032 -- LOCAT 0.162 -0.523 0.045 MARME 0.383 -0.010 0.437 REPR 0.301 0.439 0.407 PLI -0.218 TLT -0.339 Note: The eigenvalues corresponding to the first two principal components of 11 initial conditions are 4.574 and 1.941, respectively, and these two components together explain 59.23% of variability.
These regulatory agencies also have established clear protocols for measuring the QT interval and have determined the amount of drug-induced QT interval prolongation that might cause TdeP in susceptible individuals.
(8,9) In general, a drug that prolongs the QT interval by 10 ms or more (its central tendency of effect) is considered a potential cause of TdeP; drugs with higher values are labeled as even more likely to be arrhythmogenic.
Many antiarrhythmic drugs, psychiatric drugs, anti-infectives, and antihistamines prolong the QT interval and pose a risk of TdeP. Importantly, QT prolongation does not appear to be a class effect; that is, there can be a marked variation in the magnitude of QT effect among drugs with otherwise similar mechanisms of action.
Terodiline was removed from the market because it caused QT interval prolongation and TdeP. (10-12)