Anti-relapse activity of mirincamycin in the Plasmodium cynomolgi sporozoite-infected Rhesus monkey modelReport as inadecuate




Anti-relapse activity of mirincamycin in the Plasmodium cynomolgi sporozoite-infected Rhesus monkey model - Download this document for free, or read online. Document in PDF available to download.

Malaria Journal

, 13:409

First Online: 17 October 2014Received: 24 January 2014Accepted: 20 May 2014

Abstract

BackgroundMirincamycin is a close analog of the drug clindamycin used to treat Plasmodium falciparum blood stages. The clinical need to treat Plasmodium vivax dormant liver stages and prevent relapse with a drug other than primaquine led to the evaluation of mirinicamycin against liver stages in animals.

Methodscis- mirinicamycin and trans-mirinicamycin were evaluated as prophylaxis against early liver stages of Plasmodium berghei in mice and as antirelapse hypnozoiticides against Plasmodium cynomolgi in the Rhesus monkey Macaca mulatta.

ResultsMirincamycin was very effective against early liver stages of P. berghei in mice: both cis and trans enantiomers were 90-100% causally prophylactic at 3.3 mg-kg-day for 3 days orally. Both cis and trans mirincamycin, however, failed to kill dormant liver stages hypnozoites in the P. cynomolgi infected Rhesus monkey, the only preclinical hypnozoite model. Mirincamycin enantiomers at 80 mg-kg-day for 7 days orally, a dose that generated exposures comparable to that seen clinically, did not prevent relapse in any of four monkeys.

ConclusionsAlthough efficacy against early liver stages of P. berghei was thought to correlate with anti-hypnozoite activity in primates, for mirincamycin, at least, there was no correlation. The negative P. cynomolgi hypnozoite data from Rhesus monkeys indicates that mirincamycin is unlikely to have potential as a clinical anti-relapse agent.

KeywordsMalaria P. vivax Hypnozoites Relapse Mirincamycin Rhesus monkey Electronic supplementary materialThe online version of this article doi:10.1186-1475-2875-13-409 contains supplementary material, which is available to authorized users.

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Author: Susan Fracisco - Paktiya Teja-isavadharm - Montip Gettayacamin - Jonathan Berman - Qigui Li - Victor Melendez - David Saund

Source: https://link.springer.com/







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