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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996 EISSN: 1596-5996
Vol. 16, No. 4, 2017, pp. 911-917
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Bioline Code: pr17117
Full paper language: English
Document type: Research Article
Document available free of charge
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Tropical Journal of Pharmaceutical Research, Vol. 16, No. 4, 2017, pp. 911-917
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Fatal France clinical trial and the lessons learned: Application of in silico approaches to investigate the disposition of B1A10-2474 and possible safety concerns
Abdul, Mohi Iqbal Mohammed
Abstract
Purpose: Recent France clinical trial with the drug coded, B1A10-2474, turned out to be a safety failure
due to the death of a participant and several adverse events involving other participants who were on
multiple dosing. An attempt was made in this study to investigate if any possible caution could have
been detected by early predictions by in silico methods.
Methods: The physiochemical properties of B1A10-2474 were obtained using ADMETTM predictors
which were further inputted into SimCYPTM simulator to investigate the drug disposition in healthy
subjects.
Results: B1A10-2474 had linear pharmacokinetics, tendency to accumulate, follow multiple
compartment dispositions with a delayed phase of elimination, and high brain permeability with a linear
relation with blood plasma concentrations.
Conclusion: Due to high brain permeability and possible accumulation in brain with multiple dosing,
B1A10-2474 is a high alert drug. In silico approaches utilized in this study generated a safety caution
for B1A10-2474 and hence these tools can be used in early drug development processes.
Keywords
B1A10-2474, French trial, SimCYP, PBPK, ADMET, Phoenix NLME
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