Moxifloxacin population pharmacokinetics in patients with pulmonary tuberculosis and the effect of intermittent high-dose rifapentine

Abstract

We described the population pharmacokinetics of moxifloxacin and the effect of high-dose intermittent rifapentine in patients with pulmonary tuberculosis who were randomized to a continuation-phase regimen of 400 mg moxifloxacin and 900 mg rifapentine twice weekly or 400 mg moxifloxacin and 1,200 mg rifapentine once weekly. A two-compartment model with transit absorption best described moxifloxacin pharmacokinetics. Although rifapentine increased the clearance of moxifloxacin by 8% during antituberculosis treatment compared to that after treatment completion without rifapentine, it did not result in a clinically significant change in moxifloxacin exposure.

Fig 1

Illustration of the final moxifloxacin pharmacokinetic model (bottom). N₁ to N_n represents a series of hypothetical transit compartments used to model the delay in onset of absorption, and k_tr is the transit rate constant. k_a is the absorption rate constant from the hypothetical drug absorption site (depot) compartment to plasma. V_c, V_p, CL, and Q are the central and peripheral volumes of distribution and the oral and intercompartmental clearance, respectively. (Top) Visual predictive check of the final moxifloxacin pharmacokinetic model. The lower, middle, and upper solid lines are the 5th percentiles, medians, and 95th percentiles of the observed data, respectively. The shaded areas are the 95% confidence intervals for the 5th percentile, median, and 95th percentile of the simulated data. The open black circles are the observed concentrations.