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

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Diagnosis and management of malaria in the intensive care unit

“…The pharmacokinetic parameters of quinine vary among different age groups and disease states. [ 147 ] Quinine displays a rapid absorption profile when administered orally and parenterally. Furthermore, quinine is widely distributed in plasma and predominantly protein bound, especially to alpha 1 acid glycoprotein, which is an acute phase reactant protein that is often elevated in patients with acute malaria.…”

“…In settings where the ACTs are not readily available, parenteral treatment can be continued with clindamycin or doxycycline for 7 days following the last parenteral dose ( Table 4 ). [ 20 , 94 , 147 ]…”

Updates in central nervous system malaria: literature review and considerations

“…New diagnostic methods recently introduced [37 ▪ ,38–41] include rapid antigen-capture dipstick test, which could differentiate between P. falciparum and nonfalciparum malaria, and the use of a fluorescent stain to detect the plasmodia; both are fast, highly effective, and easy to perform, even without specific expertise [42 ▪ ,43,44,45 ▪ ].…”

“…Although double therapy superiority has not been demonstrated, quinine/artesunate iv association is recommended to treat severe malaria in countries were high incidence of artesunate-resistant malaria is documented (e.g. Cambodia, Laos, Thailand, Vietnam) [45 ▪ ,55,56]. Furthermore, it is strongly advised to monitor patients very cautiously, better if in an ICU.…”