Catafau Ana M, Perez Victor, Plaza Pedro, Pascual Juan-Carlos, Bullich Santiago, Suarez Marina, Penengo Maria M, Corripio Iluminada, Puigdemont Dolors, Danus Monica, Perich Javier, Alvarez Enric
Experimental Medicine, Clinical Pharmacology Discovery Medicine, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, 08005, Barcelona, Spain.
Psychopharmacology (Berl). 2006 Dec;189(2):145-53. doi: 10.1007/s00213-006-0540-y. Epub 2006 Oct 11.
To assess the paroxetine-induced serotonin transporter (SERT) occupancy (SERTocc) using in vivo (123)I-ADAM SPECT.
(123)I-ADAM SPECT was used to investigate the SERTocc induced by paroxetine in major depression disorder (MDD) patients, to compare the SERT availability in drug-free MDD patients and healthy volunteers, and to study the relationship between paroxetine plasma concentrations (Cp) and SERTocc.
Measures of SERT availability by means of (123)I-ADAM SPECT were obtained in ten MDD patients before and after 4- to 6-week treatment with paroxetine 20 mg/day. (123)I-ADAM SPECT measures of SERT availability from a group of ten previously studied age-matched healthy volunteers were used for comparison. The relationship between percentages of SERTocc and paroxetine Cp was studied using an E (max) model.
Mean SERTocc values were 66.4 +/- 9.5% in midbrain, 63.0 +/- 9.6% in thalamus, and 61.3 +/- 10.9% in striatum. No significant differences in SERTocc were found among these three regions. No significant differences in mean SERT availability were found in any region between drug-free MDD patients (midbrain = 1.14 +/- 0.15; thalamus = 0.85 +/- 0.13; striatum = 0.70 +/- 0.07) and healthy volunteers (midbrain = 1.19 +/- 0.22; thalamus = 0.96 +/- 0.14; striatum = 0.67 +/- 0.15). The E (max) model returned a SERTocc(max) = 70.5% and a Cp(50) = 2.7 ng/ml.
Using (123)I-ADAM SPECT, treatment with paroxetine 20 mg/day leads to more than 60% SERTocc on average in cerebral regions with known high SERT density. Data from this study do not support the existence of SERT availability differences between drug-free MDD patients and healthy volunteers. Finally, the E (max) model is suitable for the study of paroxetine Cp relationship to (123)I-ADAM SPECT-measured SERTocc. This approach may be useful for pharmacokinetic-pharmacodynamic relationships in drug development.
使用体内（123）I-ADAM单光子发射计算机断层扫描（SPECT）评估帕罗西汀诱导的5-羟色胺转运体（SERT）占有率（SERTocc）。
采用（123）I-ADAM SPECT研究帕罗西汀在重度抑郁症（MDD）患者中诱导的SERTocc，比较未服用药物的MDD患者和健康志愿者的SERT可用性，并研究帕罗西汀血药浓度（Cp）与SERTocc之间的关系。
对10例MDD患者在接受20mg/天帕罗西汀治疗4至6周前后，通过（123）I-ADAM SPECT测量SERT可用性。使用一组先前研究的10名年龄匹配的健康志愿者的（123）I-ADAM SPECT测量的SERT可用性进行比较。使用E（max）模型研究SERTocc百分比与帕罗西汀Cp之间的关系。
中脑的平均SERTocc值为66.4±9.5%，丘脑为63.0±9.6%，纹状体为61.3±10.9%。这三个区域之间的SERTocc没有显著差异。在未服用药物的MDD患者（中脑=1.14±0.15；丘脑=0.85±0.13；纹状体=0.70±0.07）和健康志愿者（中脑=1.19±0.22；丘脑=0.96±0.14；纹状体=0.67±0.15）之间，任何区域的平均SERT可用性均无显著差异。E（max）模型得出SERTocc（max）=70.5%，Cp（50）=2.7ng/ml。
使用（123）I-ADAM SPECT，20mg/天的帕罗西汀治疗可使已知SERT密度高的脑区平均SERTocc超过60%。本研究数据不支持未服用药物的MDD患者与健康志愿者之间存在SERT可用性差异。最后，E（max）模型适用于研究帕罗西汀Cp与（123）I-ADAM SPECT测量的SERTocc之间的关系。这种方法可能有助于药物开发中的药代动力学-药效学关系研究。
