Concerns regarding exposure-response relationship for safety
evaluation
Exposure-response analysis is also a focus of FDA and EMA concerns for
safety evaluation. All antimicrobial agents should be evaluated for
their safety profile in general and special populations by analyzing the
correlation between dose/exposure and the safety endpoints and adverse
reactions defined in clinical trials. In the example of ceftaroline
fosamil, QT interval prolongation was considered as a safety endpoint in
the exposure-response analysis [36]. One more example, voriconazole
is metabolized by cytochrome P450 isozymes CYP2C19, CYP2C9 and CYP3A4
and these P450 isozymes are inhibited by voriconazole. So, if patients
use the inhibitors or inducers of these isozymes, voriconazole should be
prescribed cautiously, especially in the patients receiving concomitant
treatment which are associated QT prolongation [37].