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Objective: To evaluate the efficacy and side effects of artemether combined with primaquine in the treatment of falciparum malaria., Methods: Randomization and comparison methods were used in 121 falciparum malaria cases in the Republic of Central Africa. Sixty-one cases were treated with artemether combined with primaquine (Group A used artemether orally, Group B used artemether intramuscularly). And 60 cases received single artemether (Group C used artemether orally, Group D used artemether intramuscularly) were taken as control., Results: In Group A and B the mean fever clearance time were 47.6 +/- 15.7 and 36.9 +/- 10.7 hours, clinical cure rates 84.4% and 100%, relapse rates 6.3% and 3.4%, respectively. In Group C and D the mean fever clearance time were 48.2 +/- 18.4 and 42.2 +/- 9.5 hours, clinical cure rates 90.1% and 96.3%, relapse rates 21.2% and 18.5%, respectively. Side effects in cases of all groups were mild., Conclusion: Artemether combined with primaquine and single artemether(via both routes) showed good therapeutic effects in falciparum malaria cases, while artemether combined with primaquine was more effective than single artemether in reducing relapes rate of malaria.

Objective: To investigate the activity of daphnetin(DPNT) against the exo-erythrocytic stage of rodent malaria., Methods: Groups of ten male ICR mice were infected by intraperitoneal injection with sporozoites of P. yoelii. Mice were administered daphnetin 0.5 hr postinfection on d0 and once per day for three additional consecutive days(d1-d3) by the i.g. route. The effects of daphnetin at various dosages and those of the combination of daphnetin with primaquine were assessed by the number of mice with negative Giemsa-stained slides from tail blood on the seventh day after infection and by the average number of red blood cells (RBC) infected in 1,000 RBC observed on the eleventh or twelfth day after infection. We also observed the effect of daphnetin on the concentration of Hb in ICR mice., Results: Daphnetin exhibited no detectable antimalarial effect on the exo-erythrocytic stage of P. yoelii, while the antimalarial efficacy of DPNT 50 mg/(kg.d) combined with 5 mg/(kg.d) PQ, was comparable to PQ 10 mg/(kg.d) x 4 d i.g. in mice infected with sporozoites of P. yoelii. The concentration of Hb in ICR mice administered with DPNT 50 mg/(kg.d) x 4 d decreased on the eighth day after administration., Conclusion: Daphnetin alone showed no anti-exoerythrocytic activity in vivo. The combination of DPNT 50 mg/(kg.d) with PQ 5 mg/(kg.d) showed promising antimalarial efficacy comparable to that of PQ 10 mg/(kg.d). Administration of DPNT caused anemia in ICR mice.

We have developed a method to estimate primaquine (PQ) and hepatic targeting antimalarial agent neoglycoalbumin-primaquine (NGA PQ) in whole blood and liver of mice by sensitive and selective high-performance liquid chromatography. The primaquine was extracted out with ether from the basified biological samples in the PQ diphosphate group or from the samples which were acidic hydrolyzed then basified in NGA-PQ group. The extracts were evaporated under N2 then dissolved in the mobile phase. A linear chain analogue of primaquine was used as the internal standard. The samples were injected into the normal phase silica column with chloroform: methanol:ammonia solution (86.8:12.5:0.7,V/V/V) as mobile phase and detected at 254 nm. The average recovery of the method was 100.09 +/- 3.46 (mean +/- s)%; the CV of within-day and between-day were 2.7%-6.13% (n = 5) and 8.32%-13.56% (n = 9) respectively; in PQ group and NGA-PQ group, the PQ concentrations ranged from 10-20,000 ng/ml blood or 1g. liver respectively, and they all yielded a good linear relationship with the peak height ratios. No endogeneous interference was found in chromatograms of biological samples.

Target-primaquine (TPQ)--the primaquine entrapped by galactosylneoglycoalbumin (G-NGA), was given intravenously (iv) to Wistar rats 2 h after sporozoite inoculation. The sporozoite viability (SPV) of TPQ 20 mg/kg group was revealed to be 1.2% 42 h after inoculation, which showed a decline of about 6% as compared to the control; besides, degeneration or retardation of development was present in 90% of EEF. In TPQ 10 mg/kg and PQ 20 mg/kg groups, the SPV were 2.8% and 5.0%, respectively, showing drops by 15% and 26% as compared with that of the control. Degeneration or retardation in development was also visible in about half of the EEF. In mice which were treated iv with TPQ 10 mg/kg or PQ 20 mg/kg 2 h after sporozoite inoculation, the prepatent periods were delayed markedly as compared with that of the control. Parasitemia did not appear in 2 mice in 10 mg/kg TPQ group further indicated the effectiveness of the drug. The results suggest that the anti-EEF effect of TPQ is apparently more promising than that of PQ.