Could clozapine’s well known peripherally-induced severe side-effects in schizophrenia patients be minimised by Intranasal administration?
Professor Darryl Eyles
Queensland Brain Institute
University of Queensland
Title: Could clozapine’s well known peripherally-induced severe side-effects in schizophrenia patients be minimised by Intranasal administration?
Abstract: Clozapine is the most effective antipsychotic drug for schizophrenia, yet it has severe debilitating metabolic, gut and potentially lethal immune-related side effects. Indeed, our lab was the 1st to show how clozapine radically alters the gut microbiome and metabolome in patients when compared to other antipsychotics.
Many of clozapine’s side effects are peripherally mediated. Intranasal (IN) drug delivery offers a direct route to the brain which largely avoids the periphery. My lab has partnered with pharmaceutical chemists at PACE who have managed to package clozapine in a new way that allows sustained IN delivery directly to the brain. In this talk I will show that IN delivery of clozapine to rats achieves comparable drug levels in brain at a fraction of the oral dose needed to achieve the same level, has minimal peripheral distribution or active metabolites and produces both acute and long-term antipsychotic actions. I will also present some ongoing study data suggesting the IN route may reduce the well-known diabetes-like symptoms induced by oral clozapine.
We had hoped to have patient tolerability data for the vehicle by the time of this seminar however there are “governance” impediments. However, if we show the vehicle is well tolerated in patients and when all preclinical metabolic/immune/gut health study data is in we hope to move to phase 1 trials in treatment-resistant patients.
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Neuroscience seminars at the QBI play a major role in the advancement of neuroscience in the Asia-Pacific region. The primary goal of these seminars is to promote excellence in neuroscience through the exchange of ideas, establishing new collaborations and augmenting partnerships already in place.
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