AB 26. Comparison of pharmacokinets of moxifloxacin between patients with drug-resistant and multi-drug resistant pulmonary tuberculosis

Background: Moxifloxacin is a potent bactericidal and sterilizing antituberculous drug that is currently used as part of the therapeutic regimen in cases of drug resistant (DR) and multi-drug resistant (MDR) tuberculosis (TB). According to previous reports rifampicin reduces moxifloxacin levels by 30%. The aim of the present study was to compare moxifloxacin levels between pulmonary MDR- and DR-TB patients.
Patients and methods: Eight patients with MDR-TB (age 42.63± 16.12 years) not receiving rifampicin and six patients with DR-TB (age 45.17±9.83 years) receiving rifampicin were included in the study. All patients had normal renal and hepatic function and were receiving moxifloxacin 400 mg per os as part of their treatment. Plasma samples were collected via a peripheral venous catheter immediately before and 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours after moxifloxacin administration. Moxifloxacin concentration was determined by highperformance liquid chromatography (HPLC) with fluorescence detection. The maximum concentration (C_max) was estimated by direct observation of determined values at each time point and Tmax was the time where that concentration was achieved. The AUC₂₄ was calculated according to the trapezoidal rule.
Results: C_max and AUC₂₄ were 4.56±1.91 μg/mL and 37.42±15.36 μg/mL*h respectively for MDR-TB patients and 3.9±0.52 μg/mL and 41.1±6.23 μg/mL*h respectively for DR-TB patients. No statistically significant differences were observed between two groups. However, based on the standard deviations of the above values, a high variability was noted in patients with MDR-TB, in contrast to patients with DR-TB. In addition, a statistically significant difference in Tmax was observed (2.31±0.53 hours for MDR-TB patients and 1.5±0.44 hours for DR-TB patients, P=0.011).
Conclusions: Moxifloxacin levels did not seem to be affected by co-administration of rifampicin. The high variability in Cmax and AUC24 in patients with MDR-TB may be of clinical significance since some patients may not accomplish the pharmacodynamic target. The prolonged tine of achievement of Cmax that was observed in MDR-TB patients is not expected to have clinical consequences as AUC was not different in the two groups.