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Altering Antimalarial Drug Regimens May Dramatically Enhance and Restore Drug Effectiveness.

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Kay, Katherine, Hodel, EvaMaria ORCID: https://orcid.org/0000-0001-5821-1685 and Hastings, Ian ORCID: https://orcid.org/0000-0002-1332-742X (2015) 'Altering Antimalarial Drug Regimens May Dramatically Enhance and Restore Drug Effectiveness.'. Antimicrobial Agents and Chemotherapy, Vol 59, Issue 10, pp. 6419-27.

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Abstract

There is considerable concern that malaria parasites are starting to evolve resistance to the current generation of antimalarial drugs, the artemisinin-based combination therapies (ACTs). We use pharmacological modeling to investigate changes in ACT effectiveness likely to occur if current regimens are extended from 3 to 5 days or, alternatively, given twice daily over 3 days. We show that the pharmacology of artemisinins allows both regimen changes to substantially increase the artemisinin killing rate. Malaria patients rarely contain more than 10(12) parasites, while the standard dosing regimens allow approximately 1 in 10(10) parasites to survive artemisinin treatment. Parasite survival falls dramatically, to around 1 in 10(17) parasites if the dose is extended or split; theoretically, this increase in drug killing appears to be more than sufficient to restore failing ACT efficacy. One of the most widely used dosing regimens, artemether-lumefantrine, already successfully employs a twice-daily dosing regimen, and we argue that twice-daily dosing should be incorporated into all ACT regimen design considerations as a simple and effective way of ensuring the continued long-term effectiveness of ACTs.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials
QV Pharmacology > QV 4 General works
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1128/AAC.00482-15
Depositing User: Mary Creegan
Date Deposited: 19 Jan 2016 10:16
Last Modified: 19 Sep 2019 11:29
URI: https://archive.lstmed.ac.uk/id/eprint/5411

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