Verrest Luka, Dorlo Thomas P C
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 80.082, 3508 TB, Utrecht, The Netherlands.
Pharmacometrics Research Group, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Clin Pharmacokinet. 2017 Jun;56(6):583-606. doi: 10.1007/s40262-016-0467-3.
Neglected tropical diseases (NTDs) affect more than one billion people, mainly living in developing countries. For most of these NTDs, treatment is suboptimal. To optimize treatment regimens, clinical pharmacokinetic studies are required where they have not been previously conducted to enable the use of pharmacometric modeling and simulation techniques in their application, which can provide substantial advantages.
Our aim was to provide a systematic overview and summary of all clinical pharmacokinetic studies in NTDs and to assess the use of pharmacometrics in these studies, as well as to identify which of the NTDs or which treatments have not been sufficiently studied.
PubMed was systematically searched for all clinical trials and case reports until the end of 2015 that described the pharmacokinetics of a drug in the context of treating any of the NTDs in patients or healthy volunteers.
Eighty-two pharmacokinetic studies were identified. Most studies included small patient numbers (only five studies included >50 subjects) and only nine (11 %) studies included pediatric patients. A large part of the studies was not very recent; 56 % of studies were published before 2000. Most studies applied non-compartmental analysis methods for pharmacokinetic analysis (62 %). Twelve studies used population-based compartmental analysis (15 %) and eight (10 %) additionally performed simulations or extrapolation. For ten out of the 17 NTDs, none or only very few pharmacokinetic studies could be identified.
For most NTDs, adequate pharmacokinetic studies are lacking and population-based modeling and simulation techniques have not generally been applied. Pharmacokinetic clinical trials that enable population pharmacokinetic modeling are needed to make better use of the available data. Simulation-based studies should be employed to enable the design of improved dosing regimens and more optimally use the limited resources to effectively provide therapy in this neglected area.
被忽视的热带病（NTDs）影响着超过10亿人，这些人主要生活在发展中国家。对于大多数此类被忽视的热带病，治疗效果并不理想。为了优化治疗方案，在之前未开展过临床药代动力学研究的情况下，需要进行此类研究，以便在应用中能够使用药代动力学建模和模拟技术，这会带来诸多显著优势。
我们的目标是对所有关于被忽视的热带病的临床药代动力学研究进行系统综述和总结，评估药代动力学在这些研究中的应用情况，并确定哪些被忽视的热带病或哪些治疗方法尚未得到充分研究。
对PubMed进行系统检索，查找截至2015年底所有描述药物在治疗患者或健康志愿者的任何一种被忽视的热带病时的药代动力学情况的临床试验和病例报告。
共识别出82项药代动力学研究。大多数研究纳入的患者数量较少（只有5项研究纳入了超过50名受试者），仅有9项（11%）研究纳入了儿科患者。很大一部分研究并非近期开展的；56%的研究在2000年之前发表。大多数研究采用非房室分析方法进行药代动力学分析（62%）。12项研究使用基于群体的房室分析（15%），8项（10%）还进行了模拟或外推。在17种被忽视的热带病中，有10种没有或仅有极少的药代动力学研究。
对于大多数被忽视的热带病，缺乏充分的药代动力学研究，且基于群体的建模和模拟技术尚未普遍应用。需要开展能够进行群体药代动力学建模的药代动力学临床试验，以便更好地利用现有数据。应采用基于模拟的研究来设计更优给药方案，并更有效地利用有限资源，为这一被忽视领域提供有效治疗。
