Pharmacokinetics of dimemorfan phosphate foIIowing singIe and muItipIe-dose oraI administration in heaIthy Chinese voIunteers / 中国药科大学学报

ABSTRACT

An LC-MS/MS method was developed to investigate the pharmacokinetic parameters in healthy Chi-nese volunteers following single and multiple oral administration of dimemorfan phosphate. In the Single-dose study,two-period and crossover study was conducted in 12 healthy volunteers,which were administered with single-dose of 10 mg or 40 mg of dimemorfan phosphate. And another 12 volunteers were administered with 20 mg. The values of AUC0-48 h,t1/2,and cmax were (11. 81 ±14. 46),(52. 60 ±96. 01 )and (34. 70 ±29. 59)ng. h/mL,(12. 11 ±2. 54),(12. 16 ±2. 01)and (12. 77 ±1. 27)h,and (0. 9653 ±0. 8178),(3. 150 ±3. 451)and (2. 167 ±1. 650)ng/mL for 10 mg,40 mg and 20 mg oral administration. The same 12 healthy volunteers as the group of single-dose of 20mg were participated in multiple-dose study,which were administered dimemorfan phos-phate 20 mg,three-time a day until the day-8,showed AUC0-48 h,t1/2,and cmax were (115. 9 ±135. 2)ng.h/mL, (11. 22 ±1. 61)h,and (7. 418 ±7. 010)ng/mL. The accumulation parameter Rcmax and RAUC was (3. 14 ±1. 34) and (3. 38 ±1. 22),respectively. Dose proportional of cmax and AUC was not concluded ranging from 10 mg to 40 mg after confidence interval criteria method. An accumulation was occurred after multiple -dose administra-tion with the consequence. And the results demonstrated significant individual difference.