SAFETY & PHARMACOKINETIC STUDY OF TOMOXETINE HYDROCHLORIDE IN PEDIATRICS

本研究的主要目的是评价盐酸托莫西汀治疗经DSM-IV定义的注意缺陷多动障碍儿童患者的安全性和有效性。 盐酸托莫西汀的血浆浓度提供了体内药物存在的测量。 本研究的目的是比较儿童患者中达到的稳态血浆浓度和药代动力学与既往药代动力学研究中成人患者中达到的稳态血浆浓度和药代动力学。 本研究中收集的信息将允许评估在儿科患者中达到稳态血浆浓度所需的剂量调整，该稳态血浆浓度与成人患者中达到的稳态血浆浓度相对应，并将确定在减少注意缺陷多动障碍症状方面提供最大治疗获益的剂量范围。初步研究结果包括托莫西汀对儿童注意缺陷多动障碍症状的强大有效性，以及令人放心的安全性和耐受性数据。 在方案的11周剂量范围研究组中，研究者能够确定最佳有效剂量约为2 mg/kg。 对药代动力学数据的初步分析显示，成人中托莫西汀的药代动力学特征与托莫西汀的药代动力学特征非常相似。 这些数据允许设计一项大型的、行业赞助的托莫西汀对照试验。

The primary objectives of this tudy are to evaluate the safety and effectiveness of tomoxetine hydrochloride in pediatric patients who have been diagnosed with attention deficit-hyperactivity disorder as defined by the DSM-IV. Plasma concentrations of tomoxetine hydrocloride provide a measurement of the presence of the drug in the body. An aim of this study is to compare the steady-state plasma concentrations achieved and pharmacokinetics attained in pediatric patients, to the steady-state plasma concentrations achieved, and pharmacokinetics attained in adult patients from prior pharmacokinetic studies. The information collected in this study will permit an assessment of dosage modification necessary to achieve steady-state plasma concentrations in pediatric patients corresponding to those achieved in adult patients, and will identify a dose range that provides maximum therapeutic benefit in the reduction of symptoms of attention deficit-hyperactivity disorder. Preliminary findings include robust effectiveness of tomoxetine for attention deficit-hyperactivity disorder symptoms in children, as well as reassuring safety and tolerability data. In the 11 week, dose ranging arm of the protocol, the investigators were able to establish an optimal effective dose of ~2 mg/kg. A preliminary analysis of the pharmacokinetic data reveals a close parallel to the phaarmacokinetic profile of tomoxetine in adults. This data has permitted the design of a large, industry sponsored controlled trial of tomoxetine.