Pharmacokinetics and Tolerability of Buspirone during Oral Administration to Children and Adolescents with Anxiety Disorder and Normal Healthy Adults

Salazar, Daniel E.; Frackiewicz, Edyta J; Dockens, Randy C.; Kollia, Georgia; Fulmor, I. Edgar; Tigel, Phillip D.; Uderman, Howard D.; Shiovitz, Thomas; Sramek, John J.; Cutler, Neal R.

doi:10.1177/00912700122012823

Cited by 45 publications

(22 citation statements)

References 12 publications

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“…In these studies that utilized 15–60 mg of buspirone per day, no significant differences between buspirone and placebo were noted for GAD symptoms [BMS, 2010]. In addition, pharmacokinetic studies of this agent revealed plasma exposure to buspirone (and its active metabolite, 1‐(2‐pyrimidinyl)‐piperazine, [1‐PP]) were equivalent or greater in pediatric patients than in adults …”

Section: Neuropharmacology Of Pediatric Gadmentioning

confidence: 99%

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Establishing the Neurobiologic Basis of Treatment in Children and Adolescents With Generalized Anxiety Disorder

et al. 2012

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Generalized anxiety disorder (GAD) is associated with significant morbidity in children and adolescents, yet only recently have the neuropharmacology and neurophysiology of this condition been studied in youth. Accumulating data suggest structural and functional abnormalities within the brain's fear networks in youth with GAD. Additionally, seven studies examined the efficacy of medications that modulate this system and, in some cases, the direct effects of these medications on structures within these networks (e.g. amygdala, ventrolateral prefrontal cortex [VLPFC]). In this review, we summarize the extant functional, functional connectivity, and structural neuroimaging data in children and adolescents with GAD. In addition, data concerning selective serotonin reuptake inhibitors (SSRIs), selective serotonin norepinephrine reuptake inhibitors (SSNRIs), atypical anxiolytics, benzodiazepines, and psychotherapy are reviewed in the context of the neurophysiology of pediatric GAD. The existing data suggest abnormal activity within the amygdala, VLPFC, and anterior cingulate cortex, as well as the possibility of impaired connectivity among these brain regions. In addition to numerous cognitive behavioral therapy (CBT) trials, five randomized, controlled psychopharmacologic trials primarily in youth with GAD suggest that SSRIs and SSNRIs are effective for this condition. These findings also raise the possibility that functional activity within the amygdala and VLPFC may be altered following successful treatment.

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Section: Neuropharmacology Of Pediatric Gadmentioning

confidence: 99%

“…In addition, pharmacokinetic studies of this agent revealed plasma exposure to buspirone (and its active metabolite, 1-(2-pyrimidinyl)-piperazine, [1-PP]) were equivalent or greater in pediatric patients than in adults. [42]…”

Section: Buspironementioning

confidence: 99%

Establishing the Neurobiologic Basis of Treatment in Children and Adolescents With Generalized Anxiety Disorder

et al. 2012

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“…One open trial in youth with a variety of anxiety disorders showed significant improvements in anxiety ratings and minimal side effects [76]. An industry-sponsored clinical trial showed that buspirone may be better tolerated at lower doses in anxious children (5-7.5 mg twice daily) than anxious adolescents (5-30 mg twice daily) [77]. Common side effects were lightheadedness, headache, and dyspepsia.…”

Section: Other Medicationsmentioning

confidence: 99%

Assessment and Treatment of Anxiety Disorders in Children and Adolescents

Connolly

Suárez

Sylvester

2011

Curr Psychiatry Rep

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This article reviews the current screening and assessment tools for anxiety disorders in children and adolescents, as well as evidence-based treatment interventions for these disorders. The following anxiety disorders are discussed: separation anxiety disorder, generalized anxiety disorder, specific phobia, panic disorder, social anxiety disorder (social phobia), and selective mutism. There are several well-studied screening and assessment tools to identify childhood anxiety disorders early and differentiate the various anxiety disorders. Evaluations of baseline somatic symptoms, severity, and impairment ratings of the anxiety disorders, and collecting ratings from several sources is clinically helpful in assessment and treatment follow-up. Cognitive-behavioral therapy (CBT) has been extensively studied and has shown good efficacy in treatment of childhood anxiety disorders. A combination of CBT and medication may be required for moderate to severely impairing anxiety disorders and may improve functioning better than either intervention alone. Selective serotonin reuptake inhibitors are currently the only medications that have consistently shown efficacy in treatment of anxiety disorders in children and adolescents. Despite proven efficacy, the availability of CBT in the community is limited. Current research is focusing on early identification of anxiety disorders in community settings, increasing the availability of evidence-based interventions, and modification of interventions for specific populations.

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“…Exposure to PmP was dose-proportional, and the variability in buspirone pharmacokinetics was so wide that no firm conclusions could be drawn regarding nonlinearity of this drug in these populations [94]. Exposure to PmP was dose-proportional, and the variability in buspirone pharmacokinetics was so wide that no firm conclusions could be drawn regarding nonlinearity of this drug in these populations [94].…”

Section: Other Variables Affecting the Metabolite-to-parent Drug Ratiomentioning

confidence: 99%

N-Dealkylation of Arylpiperazine Derivatives: Disposition and Metabolism of the 1-Aryl-Piperazines Formed

Caccia

2007

CDM

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In recent years several arylpiperazine derivatives have reached the stage of clinical application, mainly for the treatment of depression, psychosis or anxiety. Examples are the pyrimidinylpiperazine buspirone, the chlorophenylpiperazine derivatives nefazodone and trazodone, the dichlorophenylpiperazine aripiprazole and the benzisothiazolyl derivatives perospirone and ziprasidone. Most of them undergo extensive pre-systemic and systemic metabolism including CYP3A4-dependent N-dealkylation to 1-aryl-piperazines. These metabolites are best known for the variety of serotonin receptor-related effects they cause in man and animals, although some have affinity for other neurotransmitter receptors; others, however, are still largely unexplored despite uncontrolled use as amphetamine-like designer drugs. Once formed they distribute extensively in tissues, including brain which is the target site of most arylpiperazine derivatives, and are then primarily biotransformed by CYP2D6-dependent oxidation to hydroxylates which are excreted as conjugates; only 1-(2-benzisothiazolyl)-piperazine is more susceptible to sulfur oxidation than to aromatic hydroxylation. In studies analysing animal brain and human blood, 1-aryl-piperazine concentrations were either higher or lower than the parent compound(s), although information is available only for some derivatives. At steady state, the metabolite-to-parent drug ratios varied widely among individuals taking the same dosage of the same arylpiperazine derivative. This is consistent with the known individual variability in the expression and activity of CYP3A4 and CYP2D6. This review also surveys current published information on physiological and pathological factors affecting the 1-aryl-piperazine-to-parent drug ratios and examines the potential role of 1-aryl-piperazine formation in the pharmacological actions of the arylpiperazine derivatives that are already or will shortly be available in major markets.

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Pharmacokinetics and Tolerability of Buspirone during Oral Administration to Children and Adolescents with Anxiety Disorder and Normal Healthy Adults

Cited by 45 publications

References 12 publications

Establishing the Neurobiologic Basis of Treatment in Children and Adolescents With Generalized Anxiety Disorder

Establishing the Neurobiologic Basis of Treatment in Children and Adolescents With Generalized Anxiety Disorder

Assessment and Treatment of Anxiety Disorders in Children and Adolescents

N-Dealkylation of Arylpiperazine Derivatives: Disposition and Metabolism of the 1-Aryl-Piperazines Formed

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