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Highlight: [•] Compound naphthoquine phosphate (CO-ArNp) was assessed as a novel antischistosomal drug. [•] Single oral dose of CO-ArNp in mice harbouring juvenile Schistosoma mansoni significantly reduced worm burdens. [•] CO-ArNp dose of 600mg/kg in mice harbouring 3week old S. mansoni killed all female worms. [•] CO-ArNp at 600mg/kg in mice harbouring adult S. mansoni significantly reduced worms and egg burdens. [•] CO-ArNp has promising schistosomicidal and ovicidal effects and improved hepatic lesions. [Copyright &y& Elsevier]

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 AUC0-t and Cmax of both artemisinin (by 71% and 49%) and naphthoquine phosphate (by 135% and 104%) compared with mono-therapy. Food intake greatly increased the AUC0-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. [ABSTRACT FROM PUBLISHER]

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 (400mg of naphthoquine+1000mg 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 24h, were included in the final evaluation of the study. Mean fever clearance time, parasite clearance time were 18.2±8.6h and 34.6±14.3h, 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. [Copyright &y& Elsevier]