An integrated clinical pharmacology approach for deriving dosing recommendations in a regulatory setting: Review of recent cases in psychiatry drugs

Clinical pharmacology as an interdisciplinary science is unique in its capacity and the diversity of the methods and approaches it can provide to derive dosing recommendations in various subpopulations. This article illustrates cases where an integrated clinical pharmacology approach was used to derive dosing recommendations for psychiatry drugs within regulatory settings. The integrated approach is based on the view that once a drug is shown to be effective in the general population, it is reasonable to take into consideration other relevant findings and the use of alternative scientific tools and analysis to derive dosing recommendations in specific populations. The method provides useful means to solve the challenges of the paucity of available data and lead to clear dosing instructions. This in turn expands the benefits of any given drug to all individuals in which the drug is likely to be effective.

[1]  J. Gobburu,et al.  An Integrated Approach for Establishing Dosing Recommendations: Paliperidone for the Treatment of Adolescent Schizophrenia , 2013, Journal of clinical psychopharmacology.

[2]  S. Potkin,et al.  Efficacy and safety of lurasidone 80mg/day and 160mg/day in the treatment of schizophrenia: A randomized, double-blind, placebo- and active-controlled trial , 2013, Schizophrenia Research.

[3]  I. Zineh,et al.  CYP2D6 genotype information to guide pimozide treatment in adult and pediatric patients: basis for the U.S. Food and Drug Administration's new dosing recommendations. , 2012, The Journal of clinical psychiatry.

[4]  Ian M. Anderson,et al.  Antipsychotic-Related QTc Prolongation, Torsade de Pointes and Sudden Death , 2012, Drugs.

[5]  Jaskaran Singh,et al.  A Randomized, Double-Blind Study of Paliperidone Extended-Release in Treatment of Acute Schizophrenia in Adolescents , 2011, Biological Psychiatry.

[6]  D. Ochoa,et al.  Effects of CYP2D6 Genotype on the Pharmacokinetics, Pharmacodynamics, and Safety of Risperidone in Healthy Volunteers , 2010, Journal of clinical psychopharmacology.

[7]  J. Finsterer,et al.  Antipsychotic drugs and QT prolongation. , 2005, International clinical psychopharmacology.

[8]  J. Alderman Coadministration of scrtraline with cisapride or pimozide: an open-label, nonrandomized examination of pharmacokinetics and corrected qt intervals in healthy adult volunteers , 2005 .

[9]  J. Alderman Coadministration of sertraline with cisapride or pimozide: an open-label, nonrandomized examination of pharmacokinetics and corrected QT intervals in healthy adult volunteers. , 2005, Clinical therapeutics.

[10]  J. Swanson,et al.  Serum and brain concentrations of methylphenidate: implications for use and abuse , 2003, Neuroscience & Biobehavioral Reviews.

[11]  I. Shoulson,et al.  Acute tolerance to methylphenidate in the treatment of attention deficit hyperactivity disorder in children , 1999, Clinical pharmacology and therapeutics.

[12]  D. Flockhart,et al.  Identification and characterization of human cytochrome P450 isoforms interacting with pimozide. , 1998, The Journal of pharmacology and experimental therapeutics.

[13]  L. J. Barnhill,et al.  Paroxetine-pimozide drug interaction. , 1994, Journal of the American Academy of Child and Adolescent Psychiatry.

[14]  K. Silk,et al.  Fluoxetine-pimozide interaction. , 1993, American Journal of Psychiatry.

[15]  J. A. Gomes,et al.  ECG changes during haloperidol and pimozide treatment of Tourette's disorder. , 1987, The American journal of psychiatry.