[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.

S-1 plus cisplatin as first-line treatment of patients with advanced non-small cell lung cancer in Taiwan.

AIM: S-1 combined with cisplatin is known to be noninferior to taxanes plus platinum as the first-line treatment for patients with advanced nonsmall cell lung cancer (NSCLC) in the Japanese population. This study aimed to evaluate the efficacy and safety profiles of oral S-1 plus cisplatin (SP) in Taiwanese patients. METHODS: Patients with previously untreated stage IIIB or IV NSCLC were prospectively recruited to receive 40-60 mg of S-1 twice daily on days 1-21 plus 60 mg/m2 of cisplatin on day 8 in a 5-week cycle for up to six cycles. RESULTS: A total of 55 patients from five cancer centers in Taiwan were enrolled. Among the 46 evaluable patients, those administered with SP achieved disease control rate of 69.6% (partial response, 19.6%; stable disease, 50.0%), with median overall survival and progression-free survival (PFS) of 15.1 and 5.7 months, respectively. Moreover, a better survival trend was observed in epidermal growth factor receptor mutation-positive patients versus mutation-negative patients treated with SP (PFS, 8.6 vs 5.6 months). The most commonly observed treatment-related adverse events (AEs) were nausea (41.8%), followed by decreased appetite, anemia, and diarrhea. Grade of ≥3 AEs related to the study treatment occurred in 11 patients (20.0%). No febrile neutropenia or treatment-related death was found in this study. CONCLUSIONS: This study demonstrated that SP is an effective and safe first-line regimen for Taiwanese patients with advanced NSCLC.