Clinical pharmacokinetics of quinine and its relationship with treatment outcomes in children, pregnant women, and elderly patients, with uncomplicated and complicated malaria: a systematic review

Teerachat Saeheng,Kesara Na-Bangchang

doi:10.1186/s12936-022-04065-1

Abstract

BackgroundStandard 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.MethodsWeb 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.ResultsTwenty-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.ConclusionsThe 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.

Highlights

Standard dosage regimens of quinine formulated for adult patients with uncomplicated and compli‐ cated malaria have been applied for clinical uses in children, pregnant women, and elderly
A recent systematic review (2020) has suggested a high risk of treatment failure in uncomplicated malaria patients after quinine monotherapy, while the efficacy of quinine-clindamycin combination was comparable with artemisinin-based combination therapy (ACT) [3]
The objective of this study is to provide a systematic review of the existing information on the dose regimens and pharmacokinetics of quinine in children, pregnant women, and elderly populations, and to determine whether modification of dosage regimens in these populations is required

Summary

Introduction

Standard dosage regimens of quinine formulated for adult patients with uncomplicated and compli‐ cated 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 appro‐ priate. The objective of this study is to provide a systematic review of the existing information on the dose regimens and pharmacokinetics of quinine in children, pregnant women, and elderly populations, and to determine whether modification of dosage regimens in these populations is required

Objectives

Methods

Results

Conclusion