Relative bioavailability of two oral formulations of risperidone 2 mg: A single-dose, randomized-sequence, open-label, two-period crossover comparison in healthy Brazilian volunteers

Belotto, Karisa Cristina Rodrigues; Raposo, Nádia Rezende Barbosa; Ferreira, Aline Siqueira; Gattaz, Wagner F.

doi:10.1016/j.clinthera.2010.11.006

Cited by 8 publications

(9 citation statements)

References 13 publications

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“…These plasma concentrations were mostly measured at a late time point (>10 hours after the single‐dose administration). In addition, the model underestimated the concentrations of both the parent risperidone and its metabolite paliperidone in Belotto's study in Brazil . A possible explanation is that the absorption of the orally administered risperidone and the paliperidone formed in intestine was enhanced due to a suppressed P‐gp efflux activity at the intestine.…”

Section: Resultsmentioning

confidence: 89%

Physiologically Based Modeling Approach to Predict Dopamine D2 Receptor Occupancy of Antipsychotics in Brain: Translation From Rat to Human

Wong

Centanni

Lange

2019

The Journal of Clinical Pharma

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Receptor occupancy (RO) is a translational biomarker for assessing drug efficacy and safety. We aimed to apply a physiologically based pharmacokinetic (PBPK) modeling approach to predict the brain dopamine D2 RO time profiles of antipsychotics. Clozapine and risperidone were modeled together with their active metabolites, norclozapine and paliperidone, First, in PK‐Sim a rat PBPK model was developed and optimized using literature plasma PK data. Then, blood‐brain barrier parameters including the expression and efflux transport kinetics of P‐glycoprotein were optimized using literature microdialysis data on brain extracellular fluid (brainECF), which were further adapted when translating the rat PBPK model into the human PBPK model. Based on the simulated drug and metabolite concentrations in brainECF, drug‐D2 receptor binding kinetics (association and dissociation rates) were incorporated in MoBi to predict RO. From an extensive literature search, 32 plasma PK data sets (16 from rat and 16 from human studies) and 23 striatum RO data sets (13 from rat and 10 from human studies) were prepared and compared with the model predictions. The rat PBPK‐RO model adequately predicted the plasma concentrations of the parent drugs and metabolites and the RO levels. The human PBPK‐RO model also captured the plasma PK and RO levels despite the large interindividual and interstudy variability, although it tended to underestimate the plasma concentrations and RO measured at late time points after risperidone dosing. The developed human PBPK‐RO model was successfully applied to predict the plasma PK and RO changes observed after risperidone dose reduction in a clinical trial in schizophrenic patients.

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Section: Resultsmentioning

confidence: 89%

Physiologically Based Modeling Approach to Predict Dopamine D2 Receptor Occupancy of Antipsychotics in Brain: Translation From Rat to Human

Wong

Centanni

Lange

2019

The Journal of Clinical Pharma

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“…Even though calcium glucoheptonate was associated with a very good relative calcium absorption compared to calcium carbonate (92% at 6 hours and 89% at 12 hours post‐administration), we found that the 90% CIs of the treatment ratios of the log‐transformed values of C max and AUC 0–t were outside the recommended range of 80% to 125%. Differences in excipients, pharmaceutical formulations (effervescent tablets versus oral ampoules), or manufacturing processes may be responsible for these differences in product performance 20,22 . Indeed, it has been shown that pharmaceutical formulation can make a very large difference in bioavailability, and that the absorbability of some agents in tablet form significantly differs when taken in other oral forms such as powders, syrups, or ampoules 20,23 .…”

Section: Discussionmentioning

confidence: 99%

Relative bioavailability and pharmacokinetic comparison of calcium glucoheptonate with calcium carbonate

Wiria

Tran

Nguyen³

et al. 2020

Pharmacology Res & Perspec

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Abbreviations: AE, adverse event; AUC 0-∞ , area under the concentration-time curve from 0 to infinity; AUC 0-t , area under the concentration-time curve from 0 to time of the last measurable concentration; CI, confidence interval; C max , maximum plasma concentration; CV%, coefficient of variation; F, relative bioavailability; ICP-OES, inductively coupled plasma-optical emission spectrometry; LLOQ, lower limit of quantification; SD, standard deviation; t 1/2 , elimination half-life; T max , time to maximum plasma concentration. AbstractAdequate calcium intake is important for the prevention of bone loss and osteoporosis. For some populations such as those of Southeast Asia where calcium intake is very low, supplements represent a suitable dietary source of calcium. The objective of this study was to compare the relative oral bioavailability of calcium from calcium glucoheptonate, a highly soluble calcium salt containing 8.2% of elemental calcium, to that of calcium carbonate. A single-dose, randomized-sequence, open-label, twoperiod crossover study, with a 7-day washout period, was conducted in 24 Indonesian healthy adult volunteers. After a 12-hour (overnight) fast, subjects received either two oral ampoules of 250 mg/10 mL of calcium glucoheptonate each or one effervescent tablet of calcium carbonate containing 500 mg of elemental calcium. The relative oral bioavailability of calcium from calcium glucoheptonate as compared to calcium carbonate was 92% within 6 hours and 89% within 12 hours after study drug administration. The 90% confidence intervals for the mean test/reference ratios of the maximum plasma concentration and the area under the concentration-time curve at 12 hours post-administration were 77.09%-120.31% and 60.58%-122.30%, respectively. Five subjects experienced a total of eight adverse events which were all mild and transient; no serious adverse events or deaths were reported. These results indicate that calcium glucoheptonate is associated with a high relative bioavailability of calcium compared to calcium carbonate, and is well-tolerated. Calcium glucoheptonate might thus be a potential choice for calcium supplementation in Southeast Asian populations. K E Y W O R D Sbioavailability, calcium carbonate, calcium glucoheptonate, pharmacokinetics, Southeast Asia

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“…The percent prediction error for tmax is high (36%) for both reference and test tablet, but the value was still accordance with some published journal. Zhou et al reported that tmax of risperidone in Chinese female patients with schizophrenia was 1.6 h. Belotto et al reported that risperidone tmax in healthy Brazilian volunteers was 1.5 h, and Schaick et al reported that tmax was 1.8 h in healthy volunteers (19)(20)(21).…”

Section: Mechanistic Simulationmentioning

confidence: 99%

Developing In Vitro–In Vivo Correlation of Risperidone Immediate Release Tablet

2012

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The present study was aimed to predict the absorption profile of a risperidone immediate release tablet (IR) and to develop the level A in vitro-in vivo correlation (IVIVC) of the drug using the gastrointestinal simulation based on the advanced compartmental absorption and transit model implemented in GastroPlus™. Plasma concentration data, physicochemical, and pharmacokinetic properties of the drug were used in building its absorption profile in the gastrointestinal tract. Since the fraction absorbed of risperidone in simulation was more than 90% with low water solubility, the drug met the criteria of class II of the Biopharmaceutics Classification System. The IVIVC was developed based on the model built using the plasma data and the in vitro dissolution data in several dissolution media based on the Japanese Guideline for Bioequivalence Studies of Generic Products. The gastrointestinal absorption profile of risperidone was successfully predicted. A level A IVIVC was also successfully developed in all dissolution media with percent prediction error for Cmax and the area under the curve less than 10% for both reference and test drug.

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Relative bioavailability of two oral formulations of risperidone 2 mg: A single-dose, randomized-sequence, open-label, two-period crossover comparison in healthy Brazilian volunteers

Cited by 8 publications

References 13 publications

Physiologically Based Modeling Approach to Predict Dopamine D2 Receptor Occupancy of Antipsychotics in Brain: Translation From Rat to Human

Physiologically Based Modeling Approach to Predict Dopamine D2 Receptor Occupancy of Antipsychotics in Brain: Translation From Rat to Human

Relative bioavailability and pharmacokinetic comparison of calcium glucoheptonate with calcium carbonate

Developing In Vitro–In Vivo Correlation of Risperidone Immediate Release Tablet

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