Bioequivalence study of 2 orodispersible formulations of ondansetron 8 mg in healthy volunteers.

This study was designed to compare the rate and extent of absorption of 2 oral formulations of ondansetron (CAS 99614-02-5) 8 mg orodispersible tablets in healthy volunteers. 22 subjects were administered ondansetron orodispersible tablets of test and reference formulation in a single-dose, 2-period, 2-sequence, fasting, open-label, crossover and randomised study. Plasma concentrations were determined by LC/MS/MS. Log-transformed AUCs and Cmax values were tested for bioequivalence based on the ratios of the geometric means (test/reference). Tmax was analysed nonparametrically. The 90% confidence intervals of the geometric mean values for the test/reference ratios for AUC0-t and Cmax were within the bioequivalence acceptance range of 80-125%. According to the European Guideline [1] it may be therefore concluded that test formulation of ondansetron 8 mg orodispersible tablet is bioequivalent to the reference formulation.

Comparison of repeated-dose pharmacokinetics of prolonged-release and immediate-release torasemide formulations in healthy young volunteers.

The major aim of the study was to compare the pharmacokinetic profile of repeated-dose administration of a prolonged-release (PR) formulation of torasemide with that of an immediate-release (IR) dosage. Sixteen volunteers received one daily dose, on four consecutive days, of 10 mg of torasemide-PR or torasemide-IR in a single-blind, two-treatment, two-period, repeated-dose, cross-over, sequence-randomized clinical trial. Blood samples were collected at various time points on day 1 (single-dose) and on day 4 (repeated-dose) and torasemide concentrations were analysed by LC/MS/MS. Diuretic effect and urine electrolytes were measured. Urinary urgency was subjectively assessed by visual analogue scales. Safety and tolerability were also determined. Based on logged values, bioequivalence parameters, were: on day 1, ratio = 1.07 (90% CI 1.02-1.1), C(max) ratio = 0.69 (90% CI 0.67-0.73); and on day 4, ratio = 1.02 (90% CI 0.98-1.05), C(max) ratio = 0.62 (90% CI 0.55-0.70). PR had longer t(max) than IR and showed significantly lower fluctuations of plasma concentrations. Urine evaluations were similar with both formulations, although PR showed a lower urine volume in the first hours post-administration. Episodes of acute urinary urgency occurred later and were subjectively less intensive with PR. No significant adverse events were reported.

Bioequivalence evaluation of two strengths of risperidone tablet formulations in healthy volunteers.

OBJECTIVE: The objective of the study was to evaluate bioequivalence of two strengths (1 and 2 mg) of oral risperidone tablet formulations (test product manufactured by Vita-Invest, S.A., Barcelona, Spain, reference product manufactured by Janssen-Cilag Ltd., UK). SUBJECTS AND METHODS: In each of the 2 studies, 30 healthy volunteers were administered 1 or 2 mg, respectively, of test or reference formulation under fasting conditions in an open, two-way crossover, controlled, randomized and single-site fashion. Blood withdrawal was performed prior to dosing as well as 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 5 h, 8 h, 12 h, 16 h, 24 h, 48 h, 72 h, and 96 h after drug administration. Plasma concentrations of risperidone and its metabolite 9-hydroxy-risperidone were analyzed using LC/MS/MS. Descriptive data of AUC0-t, AUC0- yen, Cmax, and Cmax/AUC0- yen were log-transformed to evaluate bioequivalence based on the ratios of the geometric means of test and reference formulations. tmax was analyzed using nonparametric methods. RESULTS: The results show that in both studies, 1 and 2 mg formulations, the 90% confidence intervals for the geometric means ratios of the test and reference products for both the parent compound risperidone and its metabolite 9-hydroxy-risperidone were all within the bioequivalence acceptance criteria of 0.80 - 1.25 of the European CPMP and the US FDA guidelines, with the exception of tmax for risperidone parent compound in the 2 mg formulation, which was slightly suprabioequivalent for test formulation. CONCLUSION: This study demonstrated the bioequivalence between the test and the reference product of risperidone of both 1 and 2 mg formulations. Both formulations of each strength may, therefore, be prescribed interchangeably.