Journal of clinical pharmacology
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Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance. ⋯ Higher doses of moxifloxacin may be needed to achieve drug exposures required for improved clinical outcomes. Further study is, however, needed to determine the safety of proposed higher doses and clinically validated targets for drug exposure to moxifloxacin associated with improved tuberculosis treatment outcomes. We discuss in this review the evidence for the use of moxifloxacin in drug-susceptible tuberculosis and explore the role of moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with rifamycins, on tuberculosis treatment outcomes when used in first-line tuberculosis drug regimens.
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Clinical Trial
Notable Drug-Drug Interaction Between Etizolam and Itraconazole in Poor Metabolizers of Cytochrome P450 2C19.
In this study, impact of a polymorphism of CYP2C19 on drug-drug interaction (DDI) was examined for etizolam. The effect of itraconazole (a strong CYP3A inhibitor) on the pharmacokinetics of etizolam (a substrate of CYP2C19 and CYP3A) was assessed in both extensive metabolizers (EMs) and poor metabolizers (PMs) of CYP2C19. Sixteen participants (8 EMs and 8 PMs) received a single oral dose of etizolam (0.25 mg) on day 1. ⋯ In heterozygous EMs (hEMs), AUC∞ was simulated to be 2.56-fold higher with itraconazole than that in EMs without itraconazole. We found that in vitro measurements of fraction metabolized (fm ) using the liver microsome prepared from PM donors would be helpful to predict polymorphism-dependent DDIs. These results suggest that the PMs and hEMs of a polymorphic CYP would be at higher risk of DDIs relative to EMs for drugs metabolized by both polymorphic and nonpolymorphic CYPs such as etizolam.