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<br>[1]. Qu HY, Gao HZ, Hao GT, Li YY, Li HY, Hu JC, Wang XF, Liu WL, Liu ZY. Single-dose safety, pharmacokinetics, and food effects studies of compound naphthoquine phosphate tablets in healthy volunteers. J Clin Pharmacol. 2010 Nov;50(11):1310-8.
Abstract
The compound naphthoquine phosphate is a novel antimalaria drug tablet containing a fixed-dose combination of naphthoquine phosphate and artemisinin in a 1:2.5 ratio. A randomized, open study on the safety and tolerability was conducted in 28 healthy male volunteers using a single oral dose of 350 mg, 700 mg, 1400 mg, or 2100 mg of artemisinin-naphthoquine phosphate. Pharmacokinetics at the last 3 doses were examined in 30 volunteers. Food effects were also determined. Serial blood samples up to 216 hours after single oral dose administration were analyzed for plasma concentrations using a validated high-performance liquid chromatography-tandem mass spectrometry assay. The compound was well tolerated at single doses up to 2100 mg. Increased exposure to naphthoquine phosphate and artemisinin was less than dose proportional and linear. The half-life of naphthoquine phosphate was approximately 255 hours. The combination increased the AUC(0-t) and C(max) of both artemisinin (by 71% and 49%) and naphthoquine phosphate (by 135% and 104%) compared with monotherapy. Food intake greatly increased the AUC(0-t) of artemisinin with a ratio of 77% and reduced that of naphthoquine phosphate from 955 ± 352 μg·h/L under the fasted state to 446 ± 231 μg·h/L in the fed condition. The pharmacokinetics and safety profile of the drug support its continued investigation in future clinical studies.
<br>[2]. Tun T, Tint HS, Lin K, Kyaw TT, Myint MK, Khaing W, Tun ZW. Efficacy of oral single dose therapy with artemisinin-naphthoquine phosphate in uncomplicated falciparum malaria. Acta Trop. 2009 Sep;111(3):275-8.
Abstract
All artemisinin-based combination therapies (ACTs), recommended by the World Health Organization, are 3-day regimens. A considerable level of non-compliance on ACTs has been reported from some countries. The study aimed to assess the therapeutic efficacy of single dose treatment with new generation ACT containing artemisinin plus naphthoquine. An oral single dose of eight tablets (400 mg of naphthoquine+1000 mg artemisinin) of the combination drug was administered to adult uncomplicated falciparum malaria patients. Observations of fever, parasite clearance and reappearance, and other clinical manifestations were made on Days 0, 1, 2, 3, 7, 14, 21 and 28. Fifty-three adult falciparum positive cases, with fever or history of fever within the previous 24 h, were included in the final evaluation of the study. Mean fever clearance time, parasite clearance time were 18.2+/-8.6 h and 34.6+/-14.3 h, respectively. Adequate clinical and parasitological response was achieved in 52 cases, the rate being 98.1% (95% CI, 91.1-99.9). One patient was classified as late parasitological failure because of the reappearance of falciparum parasite on Day 14. The drug was well tolerated and no adverse reactions were detected in the patients. Since it is a single dose therapy, health workers can administer the drug as directly observed treatment.
<br>[3]. Wang JY, Ding DB, Li GF, Zhao JH. [Therapeutic efficacy of naphthoquine phosphate combined with artemisinine against Plasmodium knowlesi]. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2008 Dec 30;26(6):442-4.
Abstract
OBJECTIVE: To study the antimalarial activity of naphthoquine phosphate combined with artemisinine against Plasmodium knowlesi in rhesus monkey.METHODS: Monkeys were randomly divided into 9 groups (3/group). The monkeys in groups A and B were treated i.g. once daily for 3 days with 6 or 10 mg/kg of naphthoquine phosphate respectively. Those in groups C and D were treated i.g. twice for the 1st day and once for the 2nd and 3rd day with 31.6 or 100 mg/kg of artemisinine respectively. In groups E, F and G, they were treated i.g. only once with the combination of naphthoquine phosphate 10 mg/kg and artemisinine 10, 20 or 25 mg/kg respectively. Groups H and I served as controls which were treated i.g. only once with 10 mg/kg of naphthoquine phosphate and 30 mg/kg of artemisinine respectively. Parasitemia was examined beginning 24 h after drug administration. The observation lasted 105 days when no more parasite was found.RESULTS: At 24 h after drug administration, the parasite reduction rate in all groups was higher than 90%. The parasite clearance time for groups E, F and G was (56.0 +/- 16.0), (53.3 +/- 4.6), and (56.0 +/- 8.0) h respectively, more rapid than that of Group H [(69.3 +/- 4.6) h]. There were 1, 3, 3, 2, 2, and 3 monkeys in groups A, B, D, E, F, and G respectively which were cured. No monkeys were cured in groups C, H and I.CONCLUSION: The combination of naphthoquine phosphate and artemisinine is superior to the single component and the optimum proportion in the combination is 1 : 2.5 in treating P. knowlesi infection in monkeys.
<br>[4]. Wang JY, Cao WC, Shan CQ, Zhang M, Li GF, Ding DB, Shi YL, Wu BA.Naphthoquine phosphate and its combination with artemisinine. Acta Trop. 2004 Feb;89(3):375-81.
Abstract
Naphthoquine phosphate and artemisinine are two antimalarials developed in China. Both drugs have proven to be efficacious and well tolerated as monotherapy as well as in combination in patients suffering from malaria. The Co-naphthoquine, a novel antimalarial combination, is an oral fixed combination tablet of the naphthoquine phosphate and artemisinine. Artemisinin is characterised by a rapid onset of schizonticidal action and a short half-life. Parasite clearance is, however, often incomplete when it is employed as a single agent unless high dosages are used over several days, but such a regimen may reduce patient compliance and increase the danger of toxicity. Naphthoquine phosphate, by contrast, has a slower onset of action and a longer half-life, associated with a low recrudescence rate. The two components act synergistically in animal, and clinically provide more rapid relief of symptoms and a higher cure rate than either component alone. The combination tablet was initially developed by the Academy of Military Medical Sciences (AMMS), Beijing, China.
<br>[5]. Wang SQ, Meng F, Shen H, Wen Y, Zhuo KR, Zhu QX, Pang XJ, Lin SG, Zeng LH. Therapeutic effect of dihydroartemisinin combined with naphthoquine phosphate in patients with falciparum malaria .Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2002;20(3):180-2.
Abstract
OBJECTIVE: To observe the therapeutic efficacy of dihydroartemisinin combined with naphthoquine phosphate in patients with falciparum malaria.METHODS: Patients with Plasmodium falciparum were selected as the subjects, treated with a single dose of dihydroarteminisinin 160 mg combined with naphthoquine phosphate 400 mg (for adults) and followed up in preselective time by blood and temperature examination for 28 days after drug administration.RESULTS: 37 patients with falciparum malaria were treated and followed up. One patient had recrudescence and the cure rate in 28 days was 97.3%(36/37). The mean fever clearance time was (15.8 +/- 8.7) hours; the mean parasite clearance time was (27.6 +/- 13.2) hours; the mean reduction parasite rate in 24 hours was 96.7% +/- 26.5%. No apparent side effect was observed.CONCLUSION: A combination of dihydroartemisinin and naphthoquine is effective for the treatment of patients with falciparum malaria.
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