Bioequivalence Study of Rivastigmine 6 mg Capsules (Single Dose) in Healthy Volunteers.

OBJECTIVE: To assess the bioequivalence of generic formulation of rivastigmine (test) and Exelon (reference). METHODS: This randomized, open-label, 2-period, single-dose, 2-treatment, 2-sequence, crossover study was conducted in 40 healthy men under fed condition. Participants were randomized to receive a single dose of Exelon or rivastigmine capsule. RESULTS: A total of 31 participants completed the study. Area under the concentration-time curve from time zero to time t (AUC0- t) and area under the concentration-time curve from time zero to infinity (AUC0-∞) for Exelon (mean [standard deviation], h·ng/mL) were 126.40 (56.95) and 129.46 (59.94), respectively, while they were 122.73 (43.46) and 125.08 (45.39) for rivastigmine. Geometric mean ratios of rivastigmine/Exelon were 99.17% for AUC0- t, 98.81% for AUC0-∞, and 105% for maximum observed plasma concentration ( Cmax). The 90% confidence intervals (CIs) were 94.14% to 104.46%, 93.77% to 104.12%, and 93.08% to 118.44%, respectively. Both formulations were well tolerated. CONCLUSION: The generic and reference formulations were bioequivalent, as the 90% CIs for Cmax, AUC0- t, and AUC0-∞ were within the range of 80% to 125%.

Pharmacokinetics of fixed-dose combination of tenofovir disoproxil fumarate, lamivudine, and efavirenz: results of a randomized, crossover, bioequivalence study.

The objective of this study was to assess the bioequivalence between a fixed-dose combination of tenofovir disoproxil fumarate/lamivudine/efavirenz 300/300/600 mg and the individual innovator products. A randomized, balanced, open-label, two-sequence, two-treatment, two-period, single dose, crossover study in 48 healthy adults was conducted. Dosing was separated by a washout period of 32 days. Twenty-seven blood samples were collected in each period from pre-dose to 72 h post-dose. The data of 45 subjects were analyzed for pharmacokinetics and safety. Ninety percent CIs of geometric mean ratio on Cmax, AUC0-t, and AUC0-inf for tenofovir and lamivudine and on Cmax and AUC0-72 for efavirenz were within the acceptance criteria (80-125%). For tenofovir disoproxil fumarate, the Tmax, Kel, and t1/2 values for the test and reference products were 1.02 versus 0.91 h, 0.04 versus 0.04/h, 18.67 versus 18.46 h, respectively. For lamivudine, the Tmax, Kel, and t1/2 values were: 1.38 versus 1.30 h, 0.21 versus 0.19/h, 3.44 versus 3.91 h, respectively. For efavirenz, the Tmax values for the test and reference products were 3.71 and 3.65 h, respectively. Both the treatments were well tolerated. Our findings suggest that the tested formulation is bioequivalent to the innovators' formulations, and both treatments were well tolerated.

Bioequivalence study of cyclizine hydrochloride 50 mg tablets in healthy volunteers: a randomized, open-label, single-dose study.

BACKGROUND: Cyclizine is used in the treatment and prevention of nausea and vomiting. We aimed to demonstrate bioequivalence between two formulations of cyclizine 50 mg tablets. METHODS/RESULTS: This single-dose, two-treatment, two-period, two-sequence, open-label, randomized crossover study was conducted on 32 healthy male volunteers. The average values for Cmax, Tmax, AUC0-t and AUC0-inf were 21.50 ng/ml, 3.85 h, 423.71 ng.h/ml and 489.26 ng.h/ml, for cyclizine 50 mg (test) versus 20.39 ng/ml, 4.34 h, 410.56 ng.h/ml and 473.86 ng.h/ml for Valoid 50 mg (reference). The 90% CI of the mean ratios of Cmax (geometric mean ratio: 101.81 ng/ml), and AUC0-t (101.81 ng.h/ml) were within the bioequivalence range of 80 to 125%. Both drugs were well tolerated. CONCLUSION: Cyclizine 50 mg is bioequivalent to the reference.

Comparison of pharmacokinetics of two fenofibrate tablet formulations in healthy human subjects.

BACKGROUND: Fenofibrate is a serum lipid-lowering agent used as an adjunct to diet in patients with hypercholesterolemia and hypertriglyceridemia. The new fenofibrate tablet formulation was developed as a pharmaceutical equivalent to the marketed tablet formulation containing 145 mg. OBJECTIVE: The objective of this study was to compare the pharmacokinetics and safety of 2 tablet formulations containing 145 mg of fenofibrate (CAS number 49562-28-9) in healthy human subjects. METHODS: The study was a randomized, 2-treatment, 3-period, 3-sequence, single-dose, 3-way crossover, partial replicate bioequivalence study in healthy human subjects under fasting conditions. Eligible subjects received each treatment in a crossover manner according to the randomization schedule. Replicate dosing was conducted for the reference formulation to determine its intrasubject variability. The predose blood sample was taken within 1 hour before dosing, and serial blood sampling was performed up to 72.0 hours' postdose. The analysis of plasma samples for concentrations of fenofibric acid, the active metabolite of fenofibrate, was conducted by using a validated LC-MS/MS method. Bioequivalence was to be concluded if the 90% CIs as constructed were within the range of 80% to 125% for Cmax, AUC0-t, and AUC0-∞ for fenofibric acid. Subjects were monitored for safety and tolerability throughout the study. RESULTS: 15 healthy human subjects between 18 and 45 years of age and having body mass index between 18.5 and 30 kg/m(2) were recruited into the study. The 90% CIs for the test/reference mean ratios of the ln-transformed pharmacokinetic variables Cmax, AUC0-t, and AUC0-∞ were within the conventional bioequivalence range of 80% to 125%. Both formulations were well tolerated after a single oral dose in these healthy male subjects. CONCLUSIONS: Both fenofibrate tablet formulations demonstrated equivalent rates and extent of systemic absorption, and hence were considered bioequivalent.