[Plasma Metabolism and Protective Effect of Oral Administration of Niclosamide on Schistosoma japonicum Cercarial Invasion in Mice].

OBJECTIVE

To study the metabolism of niclosamide in plasma, and the protective effect of its oral administration on Schistosoma japonicum cercarial invasion in mice.

METHODS

Twenty-four female Kunming mice were randomly divided into 8 groups, each with 3 mice. Each mouse was treated orally with 120 mg niclosamide per kilogram of body weight (120 mg/kg). The plasma samples were collected at 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after treatment by retro-orbital blood sampling. The blood drug concentration was determined by HPLC. The pharmacokinetics parameters were calculated such as peak concentration (Cmax), peak time (Tmax), mean residence time (MRT), and elimination half life (T½). Thirty Kunming mice were randomly divided into 6 groups. Among them, 5 groups were treated orally with 40, 80, 120, 160, and 200 mg/kg niclosamide, respectively. The remaining untreated group served as control. One hour post-treatment, each mouse was infected with 40 ± 2 Schistosoma japonicum cercariae. Another 35 mice treated with 200 mg/kg niclosamide were randomly divided into 7 groups. Mice in each group were infected with 40 ± 2 S. japonicum cercariae on 0.25, 1, 4, 8, 12, and 24 h after treatment, named as group A, B, C, D, E, and F. Five untreated mice served as control (group G). All mice were sacrificed 35 days post-infection. Mean worm burden and worm reduction were calculated.

RESULTS

At a dose of 120 mg/kg niclosamide, the blood drug concentration was (0.40 ± 0.28) µg/ml at 0.25 h post-treatment, reached a peak of (0.91 ± 0.34) µg/ml at 1 h, and decreased to (0.49 ± 0.38) µg/ml at 2 h, and got close to 0 at 16 h. The mean residence time (MRT) in mice was (6.78 ± 1.47) h, and the elimination half time was (6.80 ± 7.05) h. No significant difference was found in worm burden between different dose groups and control group (P > 0.05). The mean worm burden in group A was significantly lower than that of the control (P < 0.05) with a mean worm reduction of 79.1%. And there was no significant difference in worm burden between other groups and the control (P > 0.05).

CONCLUSIONS

The blood drug concentration increases rapidly by gavage administration of 120 mg/kg niclosamide, reaching to the maximum concentration at 1 h post-treatment. It shows a certain potective effect of oral administration of 200 mg/kg niclosamide on Schistosoma japonicum cercarial invasion at 0.25 h after treatment.