Search

Background and Objective: Ornidazole, the third generation of nitroimidazole derivatives after metronidazole and tinidazole, it exerts both bactericidal and antiprotozoal effects. The purpose of this study was to evaluate the pharmacokinetic and bioequivalence of two ornidazole tablets manufactured by two different manufacturers based on their pharmacokinetic parameters., Patients and Methods: Fasted and fed healthy Chinese volunteers participated in a randomized sequence, single-dose, open-label, two-period crossover trial. There were 24 participants in both the fed study and the fasted study. Following a 7-day washout period before receiving the alternative formulation, eligible research participants were randomly assigned (1:1) to receive a single dosage of either the reference formulation or the test formulation. Following tablet administration, plasma samples were obtained over 72 h and analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) to evaluate ornidazole contents. maximum plasma concentration (C max ), time to C max (T max ), the area under the curve (AUC) from t = 0 to infinity (AUC 0-∞ ), AUC from t = 0 to the last quantifiable concentration (AUC 0-t ), half-life (t 1/2 ), and terminal elimination rate constant (z) were evaluated as pharmacokinetic (PK) parameters. The safety evaluation involved adverse events (AEs) incidence and alterations in laboratory tests (hepatic function, blood biochemistry, hematology, and urinalysis) or vital signs (temperature, pulse, and blood pressure)., Results: For the bioequivalence assessment in the fast trial, the prime PK parameters comparison between the reference and test formulation revealed that the GMR (90% CI) values for AUC 0-t , C max , and AUC 0-∞ were 100.97% (99.12-102.85%), 99.88% (90.63-110.08%), and 101.12% (99.17-103.11%), respectively. For the bioequivalence assessment in the fed trial, the key PK parameters comparison between the reference and test formulations revealed that the GMR (90% CI) values for AUC 0-t , C max , and AUC 0-∞ were 103.00% (100.94-105.11%), 101.90% (99.63-104.22%), and 102.99% (100.87-105.16%), respectively. The geometric mean ratios (GMRs) for the primary pharmacokinetic parameters (C max , AUC 0-72 , and AUC 0-∞ ) between the two formulations and the corresponding 90% confidence intervals (CIs) were all within the range of 80.00-125.00% for both the fasting and fed states. Both treatments have comparable safety profiles., Conclusion: The bioequivalence and tolerability of ornidazole tablet reference and test formulations were evaluated among healthy Chinese participants under both fasting and fed conditions. The results indicated that both formulations were bioequivalent and generally well tolerated; besides, the interaction between food and drug may affect drug pharmacokinetics., Trial Registration: CTR20212873, registered on 15 November 2021; ChiCTR2300069098, registered on 7 March 2023., (© 2024. The Author(s).)

Purpose: The aim of this study was to assess and compare the pharmacokinetic (PK) properties and bioequivalence of montelukast sodium chewable tablets prepared by two different manufacturers in healthy Chinese volunteers to obtain adequate PK evidence for the registration approval of the test formulation., Patients and Methods: A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR20182362). Eighteen subjects each were selected for a fasted study and a fed study. Eligible participants were randomly assigned in a 1:1 ratio to receive a single dose of the reference formulation or the test formulation, followed by a 5-day washout period and the administration of the alternate formulation. Plasma samples were collected over a 24-hour period following tablet administration and analyzed for montelukast contents by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The PK parameters, such as maximum serum concentration (C max ), area under the curve (AUC) from t = 0 to the last quantifiable concentration (AUC 0-t ), AUC from t = 0 to infinity (AUC 0-∞ ), half-life (t 1⁄2 ), time to C max (T max ), and terminal elimination rate constant (λ z ), were evaluated. The safety assessment included changes in vital signs (blood pressure, pulse, and temperature) or laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis) and the incidence of adverse events (AEs)., Results: The geometric mean ratios (GMRs) between the two formulations for the primary pharmacokinetic parameters (C max , AUC 0-24 , and AUC 0-∞ ) and the corresponding 90% confidence intervals (Cis) were all within the range of 80.00-125.00% for both the fasting and fed states. The safety profiles for both treatments were comparable., Conclusion: The PK analysis revealed that the test and reference formulations of montelukast sodium chewable tablets were bioequivalent and well-tolerated by healthy Chinese subjects., Competing Interests: Yingzi Pei and Xia Yue are affiliated with Beijing Fuyuan Pharmaceutical Co., Ltd. (formerly Beijing Wansheng Pharmaceutical Co., Ltd.). The authors report no other conflicts of interest in this work., (© 2021 Li et al.)