奥氮平
药效学
药代动力学
非定型抗精神病薬
药理学
人口
抗精神病药
精神分裂症(面向对象编程)
医学
内科学
精神科
环境卫生
作者
Lei Sun,Richard Mills,Brian M. Sadler,Bhaskar Rege
出处
期刊:CNS spectrums
[Cambridge University Press]
日期:2022-04-01
卷期号:27 (2): 241-241
标识
DOI:10.1017/s1092852922000451
摘要
A combination of olanzapine and samidorphan (OLZ/SAM) that provides the efficacy of olanzapine while mitigating weight gain was recently approved by the Food and Drug Administration for the treatment of schizophrenia and bipolar I disorder. This exploratory population pharmacokinetic-pharmacodynamic analysis evaluated potential relationships between drug exposure and treatment effects.Positive and Negative Syndrome Scale (PANSS) total score and/or bodyweight data from efficacy studies served as pharmacodynamic endpoints. Pharmacokinetic input came from predicted plasma drug concentrations using a population pharmacokinetic model for the corresponding studies. Regression and box plots were generated to investigate potential pharmacokinetic-pharmacodynamic relationships.PANSS total score and/or bodyweight records were paired with olanzapine and/or samidorphan concentrations from 1464 patients with schizophrenia. Within the clinical dose range for olanzapine (10-20 mg/day) and samidorphan (5-20 mg/day), no significant correlation was noted between (a) olanzapine concentrations and change in PANSS total score, or % change in body weight, in patients treated with OLZ/SAM or olanzapine, and (b) samidorphan concentration or samidorphan-to-olanzapine concentration ratio and % change in body weight. No meaningful difference in olanzapine and samidorphan concentrations or samidorphan-to-olanzapine concentration ratios was observed between patients with <10% and ≥10% weight gain.The antipsychotic efficacy of olanzapine was not affected by samidorphan at any concentration of olanzapine. Furthermore, olanzapine-associated weight gain did not correlate with olanzapine dose or plasma concentration. Finally, the effect of OLZ/SAM on mitigation of olanzapine-associated weight gain was not affected by intersubject variability in olanzapine and/or samidorphan plasma concentrations.Alkermes, Inc.
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