Pharmacokinetic/pharmacodynamic comparison between generic and brand-name levofloxacin based on Monte Carlo simulation

Abstract

The generic drugs are widely used due to its substantially low price. However, some generic drugs showed lower efficiency in terms of quality and clinical efficacy compared with brand-name drugs, especially for antimicrobial drugs. Levofloxacin is a fluoroquinolone antimicrobial drug with excellent antimicrobial activity and wide antimicrobial spectrum, while it is susceptible to drug resistance. Our study aims to evaluate the bioequivalence of generic and brand-name levofloxacin. The pharmacokinetic (PK) parameters (Cmax, AUC0∼24, Tmax and t1/2), pharmacodynamic (PD) parameters (in vitro antibacterial activity and the inhibition of resistant mutation), and PK/PD analysis (the probability of target attainment, PTA; the cumulative fraction of response, CFR) calculated by Monte Carlo simulation (MCS) were investigated. Our results demonstrated that compared with the generics, the brand-name levofloxacin not only had higher drug content, but also showed higher antimicrobial susceptibility, higher resistance to mutation ability and higher percentage of each dosage interval that plasma concentration of antimicrobial agents exceeded the MPC90 (mutant prevention concentrations to prevent the mutation of 90% strains) against various clinical isolates. Although the PK results showed the differences in AUC0∼24 between brand-name levofloxacin and generics were not statistically significant (p > 0.05, F-test), the MCS results showed CFR of PK/PD of brand-name drugs were higher than generics. Our results indicated that PK or PD equivalence did not imply the therapeutic equivalence, thus, we suggest to include PK/PD analysis in bioequivalence evaluation system, which is beneficial to the prediction of clinical out come with high application value.