Feasibility of a fixed-dose regimen of pyrazinamide and its impact on systemic drug exposure and liver safety in patients with tuberculosis.

ABSTRACT: Historically, dosing regimens for the treatment of tuberculosis (TB) have been proposed in an empirical manner. Dose selection has often been the result of efficacy trials in which drugs were administered regardless of the magnitude of the effect of demographic factors on drug disposition. This has created challenges for the prescription of fixed-dose combinations with novel therapeutic agents. The objectives of this investigation were to evaluate the impact of body weight on the overall systemic exposure to pyrazinamide (PZA) and to assess whether the use of one fixed dose, without adjustment according to weight, would ensure target exposure and safety requirements across the overall patient population. Using a population pharmacokinetic model, simulation scenarios were explored based on

SUBMITTER: Sahota T 

PROVIDER: S-EPMC3486525 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature