Abstract:

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（T1/2）. 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.

Key words: Niclosamide, Mouse, Pharmacokinetics, Gavage, Schistosoma japonicum, Cercaria