Bioequivalence and Pharmacokinetic Evaluation of 2 Pyrazinamide Formulations in Healthy Chinese Adults: A Single‐Dose, Open‐Label, Randomized‐Sequence, 2×2 Crossover Study

A single‐dose, open‐label, randomized‐sequence, 2×2 crossover study was conducted in healthy Chinese adults, after fasting and postprandial, to evaluate the bioequivalence of 2 pyrazinamide (PZA) formulations. Fasting and postprandial tests were conducted in 24 cases. Test‐reference and reference‐test were randomly divided into 2 sequence groups, with 12 cases in each group. The concentration of PZA in plasma was determined after 0.5 g single oral PZA test and reference formulations by the high‐performance liquid chromatography–tandem mass spectrometry method. In the fasting group, the 90% confidence intervals (CIs) of the 2 formulations maximum plasma concentration (C(max)), area under the plasma concentration–time curve (AUC) from time 0 to last detectable plasma concentration, and AUC from time 0 to infinity after logarithmic conversion were 104.8% to 121.9%, 97.7% to 101.6%, and 97.7% to 101.6%, respectively. In the postprandial group, the 90%CIs of the 2 formulations’ C(max), AUC from time 0 to last detectable plasma concentration, and AUC from time 0 to infinity after logarithmic conversion were 86.4% to 100.2%, 96% to 102%, 95.8% to 102.3%, respectively. The 90%CIs of the test/reference C(max) ratio and AUC ratio were within the acceptable range of 80.00% to 125.00% for bioequivalence under both fasting and postprandial conditions. No serious adverse events occurred during treatment with the test formulation or the reference formulation.