Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College, Thammasat University, Rangsit Campus, 99 Moo 18 Phaholyothin Road, Klong Luang District, Pathumthani, 12121, Thailand.
Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University, Pathumthani, Thailand.
Malar J. 2022 Feb 10;21(1):41. doi: 10.1186/s12936-022-04065-1.
Standard dosage regimens of quinine formulated for adult patients with uncomplicated and complicated malaria have been applied for clinical uses in children, pregnant women, and elderly. Since these populations have anatomical and physiological differences from adults, dosage regimens formulated for adults may not be appropriate. The study aimed to (i) review existing information on the pharmacokinetics of quinine in children, pregnant women, and elderly populations, (ii) identify factors that influence quinine pharmacokinetics, and (iii) analyse the relationship between the pharmacokinetics and treatment outcomes (therapeutic and safety) of various dosage regimens of quinine.
Web of Sciences, Cochrane Library, Scopus, and PubMed were the databases applied in this systematic search for relevant research articles published up to October 2020 using the predefined search terms. The retrieved articles were initially screened by titles and abstracts to exclude any irrelevant articles and were further evaluated based on full-texts, applying the predefined eligibility criteria. Excel spreadsheet (Microsoft, WA, USA) was used for data collection and management. Qualitative data are presented as numbers and percentages, and where appropriate, mean + SD or median (range) or range values.
Twenty-eight articles fulfilled the eligibility criteria, 19 in children, 7 in pregnant women, and 2 in elderly (14 and 7 articles in complicated and uncomplicated malaria, respectively). Severity of infection, routes of administration, and nutritional status were shown to be the key factors impacting quinine pharmacokinetics in these vulnerable groups.
The recommended dosages for both uncomplicated and complicated malaria are, in general, adequate for elderly and children with uncomplicated malaria. Dose adjustment may be required in pregnant women with both uncomplicated and complicated malaria, and in children with complicated malaria. Pharmacokinetics studies relevant to clinical efficacy in these vulnerable groups of patients with large sample size and reassessment of MIC (minimum inhibitory concentration) should be considered.
针对无并发症和有并发症疟疾的成年患者制定的常规剂量奎宁方案已应用于儿童、孕妇和老年人的临床用途。由于这些人群与成年人在解剖和生理上存在差异，因此为成年人制定的剂量方案可能并不适用。本研究旨在：(i) 回顾儿童、孕妇和老年人人群中奎宁药代动力学的现有信息，(ii) 确定影响奎宁药代动力学的因素，以及 (iii) 分析不同奎宁剂量方案的药代动力学与治疗结果（疗效和安全性）之间的关系。
本系统检索使用了预定义的搜索词，检索截至 2020 年 10 月发表的相关研究文章，应用了 Web of Sciences、Cochrane Library、Scopus 和 PubMed 数据库。最初通过标题和摘要筛选检索到的文章，排除不相关的文章，并根据全文进一步评估，应用预定义的入选标准。Microsoft Excel 电子表格（美国华盛顿州）用于数据收集和管理。定性数据以数字和百分比表示，在适当情况下，以平均值+标准差或中位数（范围）或范围值表示。
28 篇文章符合入选标准，其中 19 篇在儿童中，7 篇在孕妇中，2 篇在老年人中（分别有 14 篇和 7 篇关于无并发症和有并发症疟疾）。感染严重程度、给药途径和营养状况被证明是这些弱势群体中影响奎宁药代动力学的关键因素。
一般来说，针对无并发症和有并发症疟疾的推荐剂量对于无并发症疟疾的儿童和老年人是足够的。对于无并发症和有并发症疟疾的孕妇以及有并发症疟疾的儿童，可能需要调整剂量。应考虑在这些脆弱人群中进行与临床疗效相关的药代动力学研究，样本量要大，并重新评估 MIC（最低抑菌浓度）。
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