ABSTRACT
Rituximab, a chimeric human-mouse monoclonal antibody, has been used as a first-line treatment for CD20
ABSTRACT
The effect of realgar nanoparticles (NPs) on endogenous small molecules in rat kidney was analyzed by mass spectrometry-based metabolomics.The relationship between the changes of metabolites and the nephrotoxicity of realgar NPs was also discussed to provide a basis for the further toxicity study and the clinical application of realgar NPs.SD rats were randomly divided into seven groups,including control group,three doses (40,200,1 000 mg/kg) of relegar and realgar NPs groups,respectly.After 28 days of continuous intragastric administration,all rats were sacrificed and their serum and kidney samples were collected.The toxic effect of realgar NPs on kidney tissues were examined by biochemical analysis and histopathologic examination,which revealed a dosedependent nephrotoxicity induced by realgar NPs.The LC-MS and GC-MS analysis were performed for the subsequent metabolomics study.A series of 32 metabolites were found to be altered significandy in the kindey of realgar NPs treated rats,and might serve as potential nephrotoxicity biomarkers.The results of metabolic pathway analysis indicated that the nephrotoxicity of realgar NPs might be associated with the disorders of the amino acids and phosphatidic acid metabolism.
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.
