Background: Piperaquin (PQ) is an anti-malaria drug, which belong to bisquinoline class. Vietnam has successfully produced PQ (both base and phosphate) since 2004. Objective: To evaluate acute oral toxicities of Piperaquine phosphate and the fixed combination anti-malarial drug Dihydroartemisinin plus Piperaquine in mice. Subject and Method: This study was conducted at National Institute of Malariology, Parasitology and Entomology between June and October, 2005. The acute oral toxicities of piperaquine phosphate (PQP) and the fixed combination anti-malaria drug (40 mg dihydroiutemisinin plus 320 mg piperaquine phosphate (DHA-PQP), with the materials produced by Institute of chemistry) in mice were investigated. Result: PQP had a medium toxicity. Inhibition of mice's central nervous systems was the main toxicity exhibition. At the high doses of PQP, mice's convulsion was observed before their deaths. The infralethal dose (LDo), absolute lethal dose (LD100) and mean lethal dose (LD50) of PQP were 900, 2300 and 1643.98 (1537.6 \u2013 1758.92) mg/kg, respectively. The fixed combination DHA-PQP had a less toxicity than PQP powder, with LDo, LD100 and LD50 were 1400, 2800 and 2050.06 (1943.63 \u2013 2157.14) mg per kg of body weight, respectively. Conclusion: At the high doses of DHA-PQP, this combination also inhibited mice's central nervous systems. Mice convulsed strongly before their deaths. All died mice were operated for observing visually their organs such as hearts, livers, kidneys, lungs, vesicles and intestines. No abnormal signals were found.
Piperaquine phosphate ; toxicity ; Dihydroartemisinin

Background: The combination of dihydroartemisinin and piperaquine is interested because of its efficiency and safety in treating malaria. Objective: To evaluate the influences of the fixed combination anti-malarial drug dihydroartemisinin plus piperaquine in constitutions and some biochemical and haematological indices of rabbits. Subject and Method: The sub-chronic toxicity of the fixed combination anti-malarial drug of 40 mg dihydroartemisinin plus 320 mg piperaquine phosphate (DHA-PQP), with the materials produced by Institute of Chemistry, in rabbits was investigated. Rabbits were treated daily by oral route with DHA-PQP at the dose regimens of 64 and 100 mg/kg per day for 28 consecutive days. Result and Conclusion: DHA-PQP did not affect on rabbits' constitutions. Generally, all rabbits had normal ingestions, activities, and defecations. Rabbits' body weights increased regularly along the study period and significantly increased between day 28 and day 0 (P < 0.05). At the dose regimen of 64 mg/kg per day for 28 consecutive days, DHA-PQP did not change significantly rabbits' biochemical indices (including GOT, GPT, bilirubin, creatinine and protein) and haematological. These changes were insignificantly different between the treated and control groups at the same study points (P > 0.05). With the dose regimen of 100 mg/kg, the combination did not affect significantly (P>0.05) on some rabbits' biochemical and haematological indices. But hemoglobin, erythrocyte count and rate of monocytes increased significantly on day 14 comparing to that the control group (P < 0.05) and became in normal limits on day 29 (P > 0.05). Protein concentration also increased significantly on days 14 and 29 comparing to that of day 0 (P < 0.05).
Dihydroartemisinin plus piperaquine combination ; constitutions ; haematological

Background: Dihydroartemisinin 40mg and piperaquine phosphate 320mg (DHA-PQP) drug combination and piperaquin phosphate (PQP) material was first successfully produced in Vietnam \r\n', u'Objective: to study influences of the fixed combination antimalaria drug dihydroartemisinin plus piperaquine in reproductive progress of mice\r\n', u"Subjects and methods: This study was carried out at the Department of Malaria treatment and research, National Institute of Malariology, Parasitology and Entomology (NIMPE), between September, 2006 and March, 2007. The influences of the fixed combination antimalarial drug 40 mg dihydroartemisinin (DHA) plus 320 mg piperaquine phosphate (PQP), with PQP produced firstly in Vietnam, in mice's reproductive progresses were investigated in three generations (including the parent and FI, F2 child generations). \r\n", u'Results: In all three generations, study indices among the treated and control groups were not significantly different (the values P > 0.05). These indices included the rate of fecundation, numbers of fetuses of each mother mouse, numbers of offspring of each mother mouse, mean body weights of offspring. Early lethal fetuses, lately lethal fetuses, monsters and innate abnormally offspring were not found in P, FI and F2 generations. The necessary feeding - day numbers that offspring of P and F 1 generations reached their body weights about 20g were different insignificantly (the values P> 0.05) among the treated and control groups. \r\n', u'Conclusion: The combination DHA-PQP was found to cause no genome mutations in mice at the oral dose of 120 mg per kg per day for 5 consecutive days. \r\n', u'
Dihydroartemisinin ; piperaquine ; fixed combination antimalarial drug ; rate of fecundation ; early lethal fetuses ; lately lethal fetuses ; monsters and innate abnormally offspring ; genome mutations ; fetuses