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01-10-2000 | Review Articles

Pharmacokinetics of Artemisinin-Type Compounds

Authors: Visweswaran Navaratnam, Sharif Mahsufi Mansor, Nam-Weng Sit, James Grace, Qigui Li, Dr Piero Olliaro

Published in: Clinical Pharmacokinetics | Issue 4/2000

Abstract

Various compounds of the artemisinin family are currently used for the treatment of patients with malaria worldwide. They are characterised by a short half-life and feature the most rapidly acting antimalarial drugs to date. They are increasingly being used, often in combination with other drugs, although our knowledge of their main pharmacological features (including their absorption, distribution, metabolism and excretion) is still incomplete. Such data are particularly important in the case of combinations. Artemisinin derivatives are converted primarily, but to different extents, to the bioactive metabolite artenimol after either parenteral or gastrointestinal administration. The rate of conversion is lowest for artelinic acid (designed to protect the molecule against metabolism) and highest for the water-soluble artesunate. The absolute and relative bioavailability of these compounds has been established in animals, but not in humans, with the exception of artesunate. Oral bioavailability in animals ranges, approximately, between 19 and 35%. A first-pass effect is highly probably for all compounds when administered orally. Artemisinin compounds bind selectively to malaria-infected erythrocytes to yet unidentified targets. They also bind modestly to human plasma proteins, ranging from 43% for artenimol to 81.5% for artelinic acid.

Their mode of action is still not completely understood, although different theories have been proposed. The lipid-soluble artemether and artemotil are released slowly when administered intramuscularly because of the ‘depot’ effect related to the oil formulation. Understanding the pharmacokinetic profile of these 2 drugs helps us to explain the characteristics of the toxicity and neurotoxicity. The water-soluble artesunate is rapidly converted to artenimol at rates that vary with the route of administration, but the processes need to be characterised further, including the relative contribution of pH and enzymes in tissues, blood and liver. This paper intends to summarise contemporary knowledge of the pharmacokinetics of this class of compounds and highlight areas that need further research.

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Title: Pharmacokinetics of Artemisinin-Type Compounds
Authors: Visweswaran Navaratnam
Sharif Mahsufi Mansor
Nam-Weng Sit
James Grace
Qigui Li
Dr Piero Olliaro
Publication date: 01-10-2000
Publisher: Springer International Publishing
Published in: Clinical Pharmacokinetics / Issue 4/2000
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200039040-00002

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Pharmacokinetics of Artemisinin-Type Compounds

Abstract

At a glance: The ONWARDS insulin icodec trials

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Abstract

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