Journal of clinical psychopharmacology
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J Clin Psychopharmacol · Jun 2015
Randomized Controlled TrialUse of Remifentanil in a Novel Clinical Paradigm to Characterize Onset and Duration of Opioid Blockade by Samidorphan, a Potent μ-Receptor Antagonist.
A novel clinical study design was used to evaluate the blockade of a selective short-acting μ-opioid agonist (remifentanil) in 24 opioid-experienced subjects. Samidorphan (3-carboxamido-4-hydroxynaltrexone) is a novel opioid modulator with μ-antagonist properties. Objective (pupil diameter) and subjective (visual analog scale) responses to repeated remifentanil and saline infusion challenges were assessed after single oral administration of placebo (day 1) and samidorphan (day 2). ⋯ Samidorphan effects persisted beyond measurable samidorphan exposure (t½ = 7 hours). Samidorphan was associated with complete blockade of remifentanil, and the duration supports daily administration. This study used a novel approach with multiple administrations of remifentanil to successfully demonstrate a durable effect with samidorphan and a rapid and potent blockade of physiological and subjective μ-opioid effects.
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J Clin Psychopharmacol · Jun 2015
The Influence of the CYP3A4*22 Polymorphism and CYP2D6 Polymorphisms on Serum Concentrations of Aripiprazole, Haloperidol, Pimozide, and Risperidone in Psychiatric Patients.
Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of greater than 50% of the prescribed drugs. Recently, the CYP3A4*22 allele was reported to be associated with lower CYP3A4 expression and activity. Quetiapine, an antipsychotic metabolized by only CYP3A4, displayed higher serum levels in CYP3A4*22 carriers. Aripiprazole, haloperidol, pimozide, and risperidone are antipsychotics that are metabolized by CYP3A4 and CYP2D6. We investigated to which degree the CYP3A4*22 single-nucleotide polymorphism affects serum concentrations of patients receiving these drugs and compared this with the influence of CYP2D6 polymorphisms. ⋯ Heterozygous presence of CYP3A4*22 does not increase serum levels of antipsychotics metabolized by both CYP3A4 and CYP2D6, whereas CYP2D6 polymorphisms do affect serum levels to a limited extent.