Acute antidepressant response and plasma levels of bupropion and metabolites in a pediatric-aged sample: an exploratory study.
Acute antidepressant response and plasma levels of bupropion and metabolites in a pediatric-aged sample: an exploratory study.
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儿童样本中的急性抗抑郁反应以及安非他酮和代谢物的血浆水平：一项探索性研究。
DOI：
10.1097/01.ftd.0000197093.92559.7a
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发表时间：
2006
影响因子：
2.5
通讯作者：
Birmaher,Boris
中科院分区：
文献类型：
--
作者：
Daviss,WBurleson;Perel,JamesM;Brent,DavidA;Axelson,DavidA;Rudolph,GeorgeR;Gilchrist,Richard;Nuss,Sharon;Birmaher,Boris
研究抗抑郁反应和安非他酮及其代谢物的血浆水平之间的关联，产生了矛盾的结果。在年轻人中没有这样的研究。这项研究在8名男孩和8名女孩中探索了这种关联，年龄为11至17岁，作为药代动力学（PK）研究的一部分，所有人都服用安非他酮缓释剂（SR）治疗重度抑郁症（n= 6）或未另行说明的抑郁症（n= 10）。所有患者均开始接受100 mg/天的安非他酮SR早晨剂量，由于临床反应不足，大多数患者最终将剂量增加至200 mg/天。在服用规定剂量的安非他酮SR至少14天（中位数= 21天）后，受试者在早晨给药后24小时内测量了安非他酮及其代谢物的稳态系列血浆水平。共有9例受试者接受了100 mg/天剂量的PK评估，6例受试者接受了200 mg/天剂量的PK评估，4例受试者接受了两种剂量的PK评估。在这24小时的评估中，治疗精神科医生使用临床总体印象改善量表（CGI-I）对受试者的抗抑郁反应进行评级，对血浆水平不知情，但通过儿童和父母的抑郁症状评级量表和临床访谈进行通知。相对于7例无应答者，9例应答者（CGI-I≤ 2）的安非他酮（P= 0.03）、苏式氢安非他酮（P= 0.02）和赤式氢安非他酮（P= 0.02）的平均浓度曲线下面积显著较高，尤其是羟安非他酮（P= 0.006）。早晨给药后7.5小时的血浆水平达到以下临界点可区分应答者和非应答者：安非他酮≥ 37 ng/mL（P= 0.001）、羟基安非他酮≥ 575 ng/mL（P= 0.003）、苏式氢安非他酮≥ 240 ng/mL（P= 0.009）或赤式氢安非他酮≥ 45 ng/mL（P= 0.009）。这些初步研究结果表明，安非他酮和代谢产物，特别是羟基安非他酮的血浆水平，可以预测急性抗抑郁药反应的抑郁青年服用安非他酮SR。
Studies examining associations between antidepressant response and plasma levels of bupropion and its metabolites have yielded contradictory findings. There have been no such studies in youth. This study explored such associations in 8 boys and 8 girls, age 11 to 17 years, all prescribed bupropion sustained release (SR) for major depression (n= 6) or depressive disorder not otherwise specified (n= 10) as part of a pharmacokinetic (PK) study. All were started on morning doses of bupropion SR of 100 mg/day, and most eventually had doses increased to 200 mg/day because of inadequate clinical response. After taking prescribed dose of bupropion SR at least 14 days (median= 21 days), subjects had steady-state serial plasma levels of bupropion and its metabolites measured during a 24-hour period after morning doses. A total of 9 subjects underwent these PK assessments on doses of 100 mg/day, and 6 underwent these on doses of 200 mg/day, with 4 studied on both doses. In this 24-hour assessment, the treating psychiatrist rated subjects' antidepressant response using the Clinical Global Impression's Improvement scale (CGI-I), blind to plasma levels, but informed by child and parent rating scales of depressive symptoms and clinical interviews. Relative to 7 nonresponders, 9 responders (CGI-I≤ 2) had significantly higher mean areas under concentration curves for bupropion (P= 0.03), threohydrobupropion (P= 0.02), and erythrohydrobupropion (P= 0.02), and especially hyroxybupropion (P= 0.006). Plasma levels 7.5 hours after morning doses reaching the following cut points discriminated responders from nonresponders: bupropion≥ 37 ng/mL (P= 0.001), hydroxybupropion≥ 575 ng/mL (P= 0.003), threohydrobupropion≥ 240 ng/mL (P= 0.009), or erythrohydrobupropion≥ 45 ng/mL (P= 0.009). These preliminary findings suggest that plasma levels of bupropion and metabolites, particularly hydroxybupropion, may predict acute antidepressant response in depressed youths taking bupropion SR.