Clinical Study of Pyronaridine for the Treatment of Acute Uncomplicated Falciparum Malaria in Thailand

Looareesuwan, Sornchai; Kyle, Dennis E.; Viravan, C; Vanijanonta, S; Wilairatana, Polrat; Wernsdorfer, W. H.

doi:10.4269/ajtmh.1996.54.205

Cited by 72 publications

(60 citation statements)

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“…It demonstrates potent in vitro activity against erythrocytic stages of Plasmodium falciparum (8,24,26,36), retaining efficacy against CQR isolates (12,17,18). Clinical trials have shown excellent efficacy of monotherapy against multidrug-resistant falciparum malaria (14,24,25), with the early therapeutic response faster when combined with artesunate (20). Phase III studies with a coformulation of Pyramax (Shin Poong Pharmaceuticals) containing artesunate plus pyronaridine have recently been completed (34).…”

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confidence: 99%

In Vitro Activity of Pyronaridine against Multidrug-Resistant Plasmodium falciparum and Plasmodium vivax

Price

Marfurt

Chalfein

et al. 2010

Antimicrob Agents Chemother

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Pyronaridine, a Mannich base antimalarial, has demonstrated high in vivo and in vitro efficacy against chloroquine-resistant Plasmodium falciparum. Although this drug has the potential to become a prominent artemisinin combination therapy, little is known about its efficacy against drug-resistant Plasmodium vivax. The in vitro antimalarial susceptibility of pyronaridine was assessed in multidrug-resistant P. vivax (n ‫؍‬ 99) and P. falciparum (n ‫؍‬ 90) isolates from Papua, Indonesia, using a schizont maturation assay. The median 50% inhibitory concentration (IC 50 ) of pyronaridine was 1.92 nM (range, 0.24 to 13.8 nM) against P. falciparum and 2.58 nM (range, 0.13 to 43.6 nM) against P. vivax, with in vitro susceptibility correlating significantly with chloroquine, amodiaquine, and piperaquine (r s [Spearman's rank correlation coefficient] ‫؍‬ 0.45 to 0.62; P < 0.001). P. falciparum parasites initially at trophozoite stage had higher IC 50 s of pyronaridine than those exposed at the ring stage (8.9 nM [range, 0.6 to 8.9 nM] versus 1.6 nM [range, 0.6 to 8.9 nM], respectively; P ‫؍‬ 0.015), although this did not reach significance for P. vivax (4.7 nM [range, 1.4 to 18.7 nM] versus 2.5 nM [range, 1.4 to 15.6 nM], respectively; P ‫؍‬ 0.085). The excellent in vitro efficacy of pyronaridine against both chloroquine-resistant P. vivax and P. falciparum highlights the suitability of the drug as a novel partner for artemisinin-based combination therapy in regions where the two species are coendemic.

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confidence: 99%

In Vitro Activity of Pyronaridine against Multidrug-Resistant Plasmodium falciparum and Plasmodium vivax

Price

Marfurt

Chalfein

et al. 2010

Antimicrob Agents Chemother

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“…One important difference between the ACT partner drugs and artemisinins is that the former act primarily against the early to mid trophozoite stages when hemoglobin degradation is at its peak, whereas artemisinins act against trophozoites as well as the early ring-stage parasites (53,54). For PND, studies with P. falciparum field isolates and culture-adapted lines show minimal crossresistance between this agent and the other ACT partner drugs, illustrating that resistance mechanisms that have evolved to drugs such as ADQ or the related 4-aminoquinoline chloroquine have not compromised PND efficacy (35,(55)(56)(57). These studies also show no evidence of significantly reduced activity against P. falciparum parasites that have acquired resistance to ADQ, chloroquine, or other related drugs.…”

Section: Figmentioning

confidence: 99%

Evidence for Pyronaridine as a Highly Effective Partner Drug for Treatment of Artemisinin-Resistant Malaria in a Rodent Model

Henrich

Saénz

Cremers

et al. 2014

Antimicrob Agents Chemother

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The increasing prevalence in Southeast Asia of Plasmodium falciparum infections with delayed parasite clearance rates, following treatment of malaria patients with the artemisinin derivative artesunate, highlights an urgent need to identify which of the currently available artemisinin-based combination therapies (ACTs) are most suitable to treat populations with emerging artemisinin resistance. Here, we demonstrate that the rodent Plasmodium berghei SANA strain has acquired artemisinin resistance following drug pressure, as defined by reduced parasite clearance and early recrudescence following daily exposure to high doses of artesunate or the active metabolite dihydroartemisinin. Using the SANA strain and the parental drug-sensitive N strain, we have interrogated the antimalarial activity of five ACTs, namely, artemether-lumefantrine, artesunate-amodiaquine, artesunatemefloquine, dihydroartemisinin-piperaquine, and the newest combination artesunate-pyronaridine. By monitoring parasitemia and outcome for 30 days following initiation of treatment, we found that infections with artemisinin-resistant P. berghei SANA parasites can be successfully treated with artesunate-pyronaridine used at doses that are curative for the parental drug-sensitive N strain. No other partner drug combination was as effective in resolving SANA infections. Of the five partner drugs tested, pyronaridine was also the most effective at suppressing the recrudescence of SANA parasites. These data support the potential benefit of implementing ACTs with pyronaridine in regions affected by artemisinin-resistant malaria.

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“…In a clinical study performed in Thailand, high recrudescence has been observed. In-vitro assays revealed the presence of strains resistant to pyronaridine 23 [139]. In Africa, where the compound has not been used so far, it showed high activity against chloroquine-resistant field isolates (IC 50 values 0.8 -17.9 nM) [140].…”

Section: Drugs and Drug Combinations In Advanced Stages Of Clinical Smentioning

confidence: 99%

Antimalarial Drugs – What is in Use and What is in the Pipeline

Schlitzer¹

2008

Archiv der Pharmazie

131

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Malaria continues to be a potentially fatal threat to almost half of the world's population. In light of this threat, the armory to fight this disease is rather limited. Resistance against the most common and affordable antimalarials is widespread. Only few new drugs are in clinical development, most of them belong to long used classes of antimalarial drugs. This review will concisely cover the drugs which are currently in use, and describe the drug candidates which are in clinical evaluation.

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Clinical Study of Pyronaridine for the Treatment of Acute Uncomplicated Falciparum Malaria in Thailand

Cited by 72 publications

References 0 publications

In Vitro Activity of Pyronaridine against Multidrug-Resistant Plasmodium falciparum and Plasmodium vivax

In Vitro Activity of Pyronaridine against Multidrug-Resistant Plasmodium falciparum and Plasmodium vivax

Evidence for Pyronaridine as a Highly Effective Partner Drug for Treatment of Artemisinin-Resistant Malaria in a Rodent Model

Antimalarial Drugs – What is in Use and What is in the Pipeline

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