Pharmacokinetics of dimemorfan phosphate tablets in healthy Chinese volunteers

• Published in: European journal of clinical pharmacology Vol. 73; no. 6; pp. 709 - 715
• Main Authors: Shen, Yali, Luo, Zhu, Yu, Qin, Wang, Ying, Xiang, Jin, Miao, Jia
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2017; Springer Nature B.V
• Subjects: Antitussive Agents - administration & dosage; Antitussive Agents - pharmacokinetics; Area Under Curve; Asian Continental Ancestry Group; Bioavailability; Biomedical and Life Sciences; Biomedicine; Chromatography, High Pressure Liquid - methods; Dose-Response Relationship, Drug; Drug dosages; Fasting; Female; Food; Food-Drug Interactions; High-performance liquid chromatography; Humans; Kinematics; Male; Mass spectroscopy; Morphinans - administration & dosage; Morphinans - pharmacokinetics; Pharmacokinetics; Pharmacokinetics and Disposition; Pharmacology; Pharmacology/Toxicology; Phosphate; Tablets; Tandem Mass Spectrometry - methods; Young Adult; Pharmacokinetics; HPLC-MS/MS; Dimemorfan phosphate
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-017-2211-9

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, C max , AUC 0−t and AUC 0−∞ 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. T max ranged from 2.75 to 3.96 h and t 1/2 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.