Yali Shen1, Zhu Luo2, Qin Yu3, Ying Wang3, Jin Xiang3, Jia Miao3. 1. Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. 2. GCP Center / Institute of Drug Clinical Trials, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. luozhu720@163.com. 3. GCP Center / Institute of Drug Clinical Trials, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Abstract
OBJECTIVE: Investigate the pharmacokinetic properties of the antitussive dimemorfan phosphate tablets in healthy male and female Chinese volunteers after single and multiple-dose administration; and to evaluate the food-effect on pharmacokinetics of dimemorfan. METHODS:12 subjects received a single dose of 10 mg and 40 mg dimemorfan phosphate tablets, respectively in study stage 1. Another 12 subjects received a single dose of 20 mg dimemorfan phosphate tablets under fed conditions, a single dose of 20 mg dimemorfan phosphate tablets under fasting conditions and multiple-dosing of 20 mg dimemorfan phosphate tablets 3 times per day, respectively in study stage 2. The washout between each treatment was 1 week. Plasma dimemorfan was quantified by a high pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. RESULTS: After single-dosing of 10 mg, 20 mg and 40 mg dimemorfan phosphate tablets, Cmax, AUC0-t and AUC0-∞ were dose proportional, which achievd 6.19 ± 7.61 ng·mL-1, 101 ± 171 and 117 ± 210 ng·mL-1·h, respectively after single-dosing of 40 mg dimemorfan phosphate tablets. Tmax ranged from 2.75 to 3.96 h and t1/2 ranged from 10.6 to 11.4 h. After multiple-dosing of 20 mg dimemorfan phosphate tablets, the Accumulation Index (AI) was 2.65 ± 1.11. The pharmacokinetic parameters after single-dosing of 20 mg dimemorfan phosphate tablets under fed conditions were similar with those under fasting conditions. Sex did not affect the pharmacokinetics of dimemorfan phosphate tablets. CONCLUSIONS: Single-dosing of dimemorfan phosphate tablets exhibited linear kinetic characteristics. Multiple-dosing of 20 mg dimemorfan phosphate tablets 3 times per day caused obvious accumulation. No food effect or sex effect on the pharmacokinetics of dimemorfan phosphate tablets was observed. Chictr.org identifier: ChiCTR-ONC-14004851.
RCT Entities:
OBJECTIVE: Investigate the pharmacokinetic properties of the antitussive dimemorfan phosphate tablets in healthy male and female Chinese volunteers after single and multiple-dose administration; and to evaluate the food-effect on pharmacokinetics of dimemorfan. METHODS: 12 subjects received a single dose of 10 mg and 40 mg dimemorfan phosphate tablets, respectively in study stage 1. Another 12 subjects received a single dose of 20 mg dimemorfan phosphate tablets under fed conditions, a single dose of 20 mg dimemorfan phosphate tablets under fasting conditions and multiple-dosing of 20 mg dimemorfan phosphate tablets 3 times per day, respectively in study stage 2. The washout between each treatment was 1 week. Plasma dimemorfan was quantified by a high pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. RESULTS: After single-dosing of 10 mg, 20 mg and 40 mg dimemorfan phosphate tablets, Cmax, AUC0-t and AUC0-∞ were dose proportional, which achievd 6.19 ± 7.61 ng·mL-1, 101 ± 171 and 117 ± 210 ng·mL-1·h, respectively after single-dosing of 40 mg dimemorfan phosphate tablets. Tmax ranged from 2.75 to 3.96 h and t1/2 ranged from 10.6 to 11.4 h. After multiple-dosing of 20 mg dimemorfan phosphate tablets, the Accumulation Index (AI) was 2.65 ± 1.11. The pharmacokinetic parameters after single-dosing of 20 mg dimemorfan phosphate tablets under fed conditions were similar with those under fasting conditions. Sex did not affect the pharmacokinetics of dimemorfan phosphate tablets. CONCLUSIONS: Single-dosing of dimemorfan phosphate tablets exhibited linear kinetic characteristics. Multiple-dosing of 20 mg dimemorfan phosphate tablets 3 times per day caused obvious accumulation. No food effect or sex effect on the pharmacokinetics of dimemorfan phosphate tablets was observed. Chictr.org identifier: ChiCTR-ONC-14004851.
Authors: Soo-Youn Lee; Kwang Min Sohn; Ji Young Ryu; Young Ran Yoon; Jae Gook Shin; Jong-Won Kim Journal: Ther Drug Monit Date: 2006-06 Impact factor: 3.681