Presented at the conference of the American Society of Tropical Medicine and Hygiene 200

Fleckenstein, L

Piola, P

English

MSF Field Research

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Title: Pharmacokinetics, Clinical and Safety Outcomes of Pyronaridine/artesunate Treatment of Acute Plasmodium falciparum Malaria in Uganda
Author Block: Patrice Piola
1, Lawrence Fleckenstein
2
1MSF Epicentre, Mbarara, Uganda, 
2The University of Iowa, Iowa City, IA, United States
Disclosure Block:  P. Piola, None.
Pyronaridine/artesunate (Pyramax
®) is a novel treatment of Plasmodium falciparum malaria. A randomised, multicentre, Phase II, dose-ranging clinical study was conducted to assess
the safety and efficacy of fixed dose, orally administered pyronaridine and artesunate in adult patients with acute uncomplicated Plasmodium falciparum malaria. Pyronaridine
pharmacokinetics was studied in a sub-population of 16 Uganda patients. Treatment with pyronaridine/artesunate: 6+2 mg/kg (n=5), 9+3 mg/kg (n=5), 12+4 mg/kg (n=6), was once
daily for 3 days being closely matched for demographic characteristics. Pyronaridine/artesunate treatment resulted in cure at Day 28 for all patients treated with each of the dose
groups and this effect continued out to Day 42. All patients were clear of parasites by Day 2. The concentration pyronaridine in whole blood was measured using a previously validated
LC-MS method. Noncompartmental pharmacokinetic analysis yielded mean (±SD) values for Cmax of 91.9 ± 30.8, 156.8 ± 57.1 and 226.1 ± 157.5 ng/mL following 6, 9, 12 mg/kg body
weight oral doses, respectively. The corresponding values for AUC(0-infinity), T½, and Tmax were 749 ± 603, 1036 ± 286, 1134 ± 624 ng/mL*d, 19.1 ± 5.9, 15.9 ± 5.0, 14.6 ± 6.6 d, and
5.3 ± 2.0, 6.2 ± 6.3, 7.6 ± 4.9 h, respectively. The pyronaridine blood level profile shows a very pronounced distribution and elimination phase. A prominent second peak was noted in
the pyronaridine blood level profiles for some patients. The elimination half-life is longer than previously reported, resulting from a more sensitive pyronaridine assay methodology and
prolonged blood sampling. The pyronaridine Cmax (following the third dose) was lower in malaria patients compared with healthy volunteers, suggesting that malaria patients have a
larger pyronaridine volume of distribution. Pyronaridine/artesunate treatment was well tolerated in this study.
 
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Pharmacokinetics, clinical and safety outcomes of Pyronaridine/artesunate Treatment of Acute Plasmodium falciparum Malaria in Uganda

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