Mass balance and metabolism of the antimalarial pyronaridine in healthy volunteers
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- 作者：Carrie A. Morris ; Stephen R. Dueker…
- 关键词：Pyronaridine ; Mass balance ; Metabolism ; Antimalarial
- 刊名：European Journal of Drug Metabolism and Pharmacokinetics
- 出版年：2015
- 出版时间：March 2015
- 年：2015
- 卷：40
- 期：1
- 页码：75-86
- 全文大小：929 KB
- 参考文献：1. Croft, SL, Duparc, S, Arbe-Barnes, SJ, Craft, JC, Shin, CS, Fleckenstein, L, Borghini-Fuhrer, I, Rim, HJ (2012) Review of pyronaridine anti-malarial properties and product characteristics. Malar J 11: pp. 270 CrossRef
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- 出版者：Springer Paris
- ISSN：2107-0180
文摘
This was a single dose mass balance and metabolite characterization study of the antimalarial agent pyronaridine. Six healthy male adults were administered a single oral dose of 720?mg pyronaridine tetraphosphate with 800 nCi of radiolabeled 14C-pyronaridine. Urine and feces were continuously collected through 168?h post-dose, with intermittent 48?h collection periods thereafter through 2064?h post-dose. Drug recovery was computed for analyzed samples and interpolated for intervening time periods in which collection did not occur. Blood samples were obtained to evaluate the pharmacokinetics of total radioactivity and of the parent compound. Total radioactivity in urine, feces, and blood samples was determined by accelerator mass spectrometry (AMS); parent concentrations in blood were determined with LC/MS. Metabolite identification based on blood, urine, and feces samples was conducted using a combination of LC?+?AMS for identifying radiopeaks, followed by LC/MS/MS for identity confirmation/elucidation. The mean cumulative drug recovery in the urine and feces was 23.7?and 47.8?%, respectively, with an average total recovery of 71.5?%. Total radioactivity was slowly eliminated from blood, with a mean half-life of 33.5?days, substantially longer than the mean parent compound half-life of 5.03?days. Total radioactivity remained detectable in urine and feces collected in the final sampling period, suggesting ongoing elimination. Nine primary and four secondary metabolites of pyronaridine were identified. This study revealed that pyronaridine and its metabolites are eliminated by both the urinary and fecal routes over an extended period of time, and that multiple, varied pathways characterize pyronaridine metabolism.