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 present study aimed to assess the bioequivalence of a new apixaban generic with reference formulation. Twenty-six healthy volunteers were recruited for an open-label, balanced, randomized, 2-treatment, 2-sequence, 2-period, single oral dose study. Following overnight fasting, each volunteer received 5 mg of apixaban test and reference formulations as single doses, separated by a 1-week washout period. Twenty blood samples were collected at predose and multiple time points between 0.5 and 72 hours after dosing. A validated ultra-performance liquid chromatography-tandem mass spectrometry detection method following a protein precipitation step was implemented to determine apixaban concentrations. Noncompartmental analysis was used to derive the pharmacokinetic parameters, which were then compared between the test and reference products using a multivariate analysis of variance. The pharmacokinetic parameters of the test product were not statistically different from the reference product, and the 90% confidence intervals of apixaban natural log-transformed area under the concentration-time curve from time 0 to infinity, area under the concentration-time curve from time 0 to the last measurable concentration, and maximum concentration were within 80%-125% based on the bioequivalence acceptance range criteria. The test and reference formulations of apixaban are bioequivalent in healthy subjects under fasting conditions.
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
AIM AND OBJECTIVE: To evaluate the safety of two new generic ophthalmic formulations, Latanost® (latanoprost) and Latacom® (latanoprost and timolol) by utilizing the three-dimensional reconstructed human cornea-like epithelium (RhCE) tissue constructs as an in vitro model in the assessment of ocular irritation. MATERIALS AND METHODS: In vitro irritation test was conducted on Latanost® (LTN) and Latacom® (LTC) and their corresponding innovators, Xalatan® (XLT) and Xalacom® (XLC), respectively, by using RhCE. According to the OECD guidelines No. 492 on the testing of chemicals, the ophthalmic formulations were assessed via topical exposure of the formulations on in vitro RhCE tissue. Cell viability was measured by MTT assay. RESULTS: The mean cell viability percentage of LTN and XLT was 70.5 and 75.7%, respectively, whereas, for LTC and XLC, the percentage viability was 95.3 and 85.7%, respectively. The two new generic formulations (LTN and LTC) did not reduce the cell viability of the RhCE tissue to ≤60%. Thus, both can be considered as nonirritant. CONCLUSION: Both newly developed generics are nonocular irritants. CLINICAL SIGNIFICANCE: This study informs the safety assessment of new generic antiglaucoma ophthalmic solutions applicable for long-term glaucoma treatment. The formulations aim to keep eye irritation to a minimum level. HOW TO CITE THIS ARTICLE: Ng JSC, Tan YX, Alwi NAA, et al. In Vitro Toxicity Evaluation of New Generic Latanost® and Latacom® as an Ophthalmic Formulation. J Curr Glaucoma Pract 2021;15(3):139-143.
