The current study aimed to evaluate the bioequivalence of a new generic combination of simvastatin and ezetimibe with the reference formulation. An open-label, randomized, 3-period, 3-sequence, crossover study, including 60 healthy volunteers, was implemented. Participants received the test and reference formulation, each containing 20 mg of simvastatin and 10 mg of ezetimibe as a single-dose tablet, separated by a minimum of 2-week washout periods. Blood samples were collected for 20 time points from predose to 72 hours after the dose. The total ezetimibe assay was carried out using a validated liquid chromatography-tandem mass spectrometry, while unconjugated ezetimibe, simvastatin, and simvastatin ß-hydroxy acid determination was done via a validated ultra-performance liquid chromatography-tandem mass spectrometry. Each assay was preceded by a liquid-liquid extraction step. The pharmacokinetic parameters were derived using noncompartmental analysis and then compared between the reference and test formulations via a multivariate analysis of variance. No statistical difference was found in under the concentration-time curve from time 0 to the last quantifiable concentration and maximum concentration of unconjugated ezetimibe, total ezetimibe, and simvastatin between the reference and test formulations. The 90% confidence intervals of unconjugated ezetimibe, total ezetimibe, and simvastatin natural log-transformed under the concentration-time curve from time 0 to the last quantifiable concentration, and maximum concentration were in the range of 80%-125% as per the bioequivalence acceptance criteria. Therefore, the test formulation was bioequivalent to the reference formulation.
The current study aimed to assess the bioequivalence of a new branded azithromycin with the reference formulation. An open-label, randomized, 2-stage, crossover study design was implemented involving 77 healthy volunteers under fasting conditions. Each volunteer received a single dose of 250-mg azithromycin tablets test and reference formulations separated by a 21-day washout period. Twenty-two samples were collected at pre-dose and until 72 hours post-dose. Azithromycin concentrations were analyzed using a high-performance liquid chromatography-mass spectrometry validated method following a solid-phase plasma extraction. Noncompartmental analysis was carried out to estimate the pharmacokinetic parameters, which were compared between the test and reference products using a multivariate analysis of variance. The difference between Cmax and AUC0-72 of the test and reference formulation was not significant. The 94.1% confidence intervals of ln-transformed Cmax and AUC0-72 of azithromycin were within the bioequivalence acceptance limits of 80%-125%, therefore it can be concluded that the tested formulation is bioequivalent to the reference formulation.
Azithromycin , Area Under Curve , Cross-Over Studies , Healthy Volunteers , Humans , Tablets , Therapeutic Equivalency
A newly developed branded generic of a moxifloxacin (MOX) 400-mg tablet formulation was manufactured prior to this study. A bioequivalence (BE) study was done to assess the pharmacokinetics of the formulation using a randomized, open-label, 2-period crossover, 2-sequence, and single-dose experiment. Thirty healthy male volunteers were recruited. The test formulation, Flonoxin 400 mg, was compared with the reference formulation, Avelox 400 mg. The pharmacokinetic parameters of MOX were calculated based on the plasma drug concentration-time profile. Noncompartmental analysis was performed to determine its safety and tolerability. The 90% confidence intervals (CIs) were 88.5%-104.6%, 96.1%-101.1%, and 96.8%-100.7% for Cmax , AUC0-t , and AUC0-inf , respectively. All CIs were within the 80.0%-125.0% boundary, thus fulfilling the acceptable BE criteria according to the ASEAN guidelines.
Moxifloxacin , Cross-Over Studies , Healthy Volunteers , Humans , Male , Tablets , Therapeutic Equivalency
