Pharmacokinetic comparison of fast-disintegrating and conventional tablet formulations of risperidone in healthy volunteers.

BACKGROUND

Difficulties with and resistance to tablet-taking are common in all patient groups and can exacerbate compliance problems and undermine treatment efficacy. In recent years, rapidly dissolving oral drug formulations have been developed to overcome problems related to swallowing difficulties.

OBJECTIVE

The goal of this study was to evaluate the bioequivalence of a fast-disintegrating oral tablet of risperidone and the conventional oral tablet.

METHODS

This was a randomized, open-label, 2-way crossover trial in which healthy volunteers received two 0.5-mg tablets of a fast-disintegrating oral risperidone formulation and two 0.5-mg tablets of conventional oral risperidone, each in a single administration. Blood samples for pharmacokinetic analysis of the active moiety (risperidone + 9-hydroxy-risperidone), risperidone, and its active metabolite 9-hydroxy-risperidone were obtained during a 96-hour period after dosing. Safety assessments included monitoring of adverse events, hematology and biochemistry tests of the sampled blood, urinalysis, blood pressure measurements, and electrocardiography.

RESULTS

The bioequivalence assessment was based on pharmacokinetic and statistical analysis of data from 37 subjects who completed both treatment periods. The plasma concentration-time profiles of the active moiety, risperidone, and 9-hydroxy-risperidone were similar after intake of the 2 formulations. The fast-disintegrating tablet and the conventional tablet showed bioequivalence with respect to the active moiety, risperidone, and 9-hydroxy-risperidone. The 90% CIs for the mean treatment ratios of the log-transformed peak plasma concentration, area under the plasma concentration-time curve (AUC) to the last quantifiable time point, and AUC extrapolated to infinity were all within the predefined equivalence range from 80% to 125%. Twenty-eight of 50 (56%) subjects originally randomized reported adverse events, with a similar incidence for both treatments. All adverse events were mild, with somnolence and headache being the most frequently reported. No clinically relevant changes were observed in physical, biochemical, hematologic, or urinalysis variables during the study.

CONCLUSION

In this study in healthy subjects, a single administration of two 0.5-mg fast-disintegrating risperidone tablets was bioequivalent to a single administration of two 0.5-mg conventional risperidone tablets.