ABSTRACT
Monoclonal antibody ( mAb ) represents a class of therapeutics experienced dramatic development over the past 30 years. Because of the tremendous differences in physicochemical and biological properties between mAbs and small molecules, the mAb therapeutics significantly differ from the chemical drugs in pharmacokinetic characteristics and underlying mechanisms. Full understanding of those characteristics and mechanisms may efficiently guide the screening and development of mAb medi-cines, and would well support their safety evaluation and clinical dosage regimen designing. This review is to summarize pharma-cokinetics and underlying mechanisms of mAbs from the aspects of absorption, distribution and elimination, as well as the ap-proaches for prediction of mAb pharmacokinetics in humans.
ABSTRACT
Aim To study absorption characteristics of SM-1 , a novel anti-tumor agent , to provide a research basis for the druggability evaluation of SM-1 and formu-lation design. Methods Caco-2 cell monolayer model and in situ single-pass intestinal perfusion rat model were used to study the absorption characteristics of SM-1 , and the absorption of SM-1 in vivo was evaluated through absolute bioavailability study in rats. Results The results of cell monolayer model showed that cu-mulative absorption and efflux of SM-1 increased line-arly with concentration ( 10 ~40 mg · L-1 ) . There were no significant differences in Papp with different concentrations ( P>0. 05 ) . SM-1 was absorbed mainly through passive diffusion. The intestinal perfusion re-sults showed that Ka and Pef of SM-1 had no significant differences ( P > 0. 05 ) , when the concentrations ranged from 25 to 100 mg · L-1 . SM-1 entered the systemic circulation mainly via on passive diffusion, indicating it is a compound with high permeability. The absorption of SM-1 in duodenum was superior to other intestinal segments ( P 0. 05 ) . The absolute bioavailability of SM-1 in rats was 29. 3%. Conclusion The membrane perme-ability of SM-1 is high and it can be absorbed by intes-tine well. The absorption mechanism of SM-1 is pas-sive diffusion, and it possibly escapes from the efflux transporter protein. The absolute bioavailability of SM-1 in rats is low.