PK of Levofloxacin in MDR-TB Patients
PK of Levofloxacin in MDR-TB Patients
The emergence and spread of multi-drug resistant and extensively-drug resistant strains of
 Mycobacterium tuberculosis (MDR/XDR-TB) have posed a great threat to global TB control and
 elimination, limiting treatment success rate at worrisome 50% for MDR-TB. Among various
 factors contributing to the development of drug resistance, low drug exposure is well
 recognized. To overcome this, either new drugs have to be developed or the dose of currently
 used therapy be optimized, or both. Fluoroquinolones (levofloxacin and moxifloxacin) and
 aminoglycosides are important drugs in the MDR-TB treatment regimen. Development of acquired
 drug resistance to these drugs could complicate and narrow down the available options, and
 further exacerbate to pre-XDR and XDR-TB.

 Objective:

 The main objective of this prospective clinical study is to understand the pharmacokinetics
 of levofloxacin in MDR-TB patients, receiving standard dosage (750-1250mg) based on the body
 weight and correlate drug exposure, with treatment outcomes.

 Study design:

 A prospective pharmacokinetic study

 Study population: 20 MDR-TB patients

 Intervention: Patients receive once daily oral dosing of levofloxacin (750-1250mg) based on
 the body weight, under MDR-TB treatment regimen of Nepal.

 Main study parameters/end points:

 The pharmacokinetic parameters(Vd, CL, AUC etc.) of levofloxacin are the primary end points
 of the study. The Cmax/MIC and AUC0-24h/MIC ratios are the best predictive parameters for
 efficacy of levofloxacin treatment and will be estimated. Pharmacokinetics will be evaluated
 in plasma and in oral fluid
Inclusion Criteria:

 -  Patient with TB, with Mycobacterium tuberculosis by culture/ Gene Xpert

 -  Patient is 18 years or older with newly diagnosed or previously treated MDR-TB

 -  Patient with sputum smear positive for acid-fast bacilli or sputum smear negative but
 Gene Xpert (MTB/RIF) positive, and resistant to both isoniazid and rifampicin

 -  Patients with MDR-TB receiving levofloxacin as a part of MDR-TB regimen

 Exclusion Criteria:

 -  Patient with neurologic or severe extra-pulmonary manifestations of tuberculosis

 -  Pregnant women or breast feeding mothers with MDR-TB

 -  Patients with diminished renal functions or on medications for the treatment of renal
 disorders

 -  Body weight <35 kg

 -  Patients treated with aluminium- and magnesium containing antacids and ferrous
 sulphates, cimetidine and probenecid, theophylline, warfarin, zidovudine, digoxin or
 cyclosporine.