Comparative Bioavailability of Two Oral Formulations of Clozapine in Steady State Administered in Schizophrenic Volunteers Under Individualized Dose Regime

Borges, Ney Carter do Carmo; Astigarraga, Rafael Barrientos; Sverdloff, Carlos Eduardo; Galvinas, Paulo Rabelo; Borges, Bruno C.; Moreno, Ronílson Agnaldo

doi:10.2174/157488412803305849

Cited by 3 publications

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“…Many methods for evaluation of bioequivalence of clozapine formulations in plasma are available in the literature (Wohlfarth et al, 2011;da Fonseca et al, 2013;do Carmo Borges et al, 2012). Amongst the similar generic drugs commercially available at the time this study was started, Zolapin was chosen as being a potential low cost antipsychotic substance under the scrutiny of the Brazilian Health Authorities.…”

Section: Introductionmentioning

confidence: 99%

Steady-state bioequivalence study of clozapine psychotic patients in Brazil

TimÃ3teo¹,

Alves²,

Cardoso³

et al. 2016

Afr. J. Pharm. Pharmacol.

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The present work aimed to compare the relative bioavailability of Zolapin with 100 mg tablet Leponex as a reference formulation, through a simple, robust and low-cost bioequivalence assays method. The study design was multiple-dose, randomized, crossover with patients in steady-state, and was performed with 24 schizophrenic male patients. Subjects received 100 mg twice a day of either Leponex or Zolapin for 10 days. At day 10 days of each study phase, blood samples were collected at different times during 12 h after drug administration and the clozapine concentration was determined by high performance liquid chromatography (HPLC). The individual peak plasma concentrations (C max) and the area under the concentration-time curve (AUC 0-12h) ratios were calculated. The evaluated pharmacokinetic parameters were quite similar for both formulations. The 90% confidence interval for mean ratio of lnC max (0.9677 to 0.9937) and lnAUC 0-12h (0.9811 to 1.0029) were within accepted international guidelines. The results demonstrate that this methodological approach was able to identify Zolapin as bioequivalent to Leponex when orally administered, both in terms of the rate and extent of absorption, and therefore, suitable as a potential low-cost alternative to branded antipsychotic drugs.

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Section: Introductionmentioning

confidence: 99%

Steady-state bioequivalence study of clozapine psychotic patients in Brazil

TimÃ3teo¹,

Alves²,

Cardoso³

et al. 2016

Afr. J. Pharm. Pharmacol.

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Good Clinical Practice

2014

Handbook of Bioequivalence Testing

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Literature Values of Terminal Half-Lives of Clozapine are Dependent on the Time of the Last Data Point

Fang

Mosier

2014

J Pharm Pharm Sci

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The pharmacokinetics of clozapine is a subject of intensive research because of its narrow therapeutic window and susceptibility to drug-drug interactions. A systematic literature search was conducted in PubMed and Google Scholar for half-life values of clozapine in humans. Twenty-one publications were found to contain terminal half-life information of clozapine in humans along with the time of the last plasma sample. Average values of the terminal half-lives of clozapine were calculated to be 10.2, 13.2, 14.2, 18.3 and 29.2 hours with a last data point at 12, 24, 48, 72 and 120 hours, respectively. This confirms the notion that one would arrive at longer terminal half-lives when longer blood sampling times are used in pharmacokinetic studies on clozapine. “Terminal half-lives” of therapeutic agent are routinely computed and reported in literature. For drugs with a third deep compartment such as clozapine, one should remember to consider the time of the last data point when comparing the “terminal” half-life.

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Comparative Bioavailability of Two Oral Formulations of Clozapine in Steady State Administered in Schizophrenic Volunteers Under Individualized Dose Regime

Cited by 3 publications

References 0 publications

Steady-state bioequivalence study of clozapine psychotic patients in Brazil

Steady-state bioequivalence study of clozapine psychotic patients in Brazil

Good Clinical Practice

Literature Values of Terminal Half-Lives of Clozapine are Dependent on the Time of the Last Data Point

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