Absorption Characteristics of Combination Medication of Realgar and : Transport across MDCK-MDR1 Cells and Pharmacokinetics in Mice after Oral Administration.

Realgar and are clinically combined to treat varieties of leukemia. Exploring the drug-drug interactions might be beneficial to find active substances and develop new targeted drugs. This study aimed at exploring the change of arsenic concentration in mice and across MDCK-MDR1 cells and the cytotoxicity on K562 cells when realgar and were combined. In the presence or absence of , pharmacokinetics and cell-based permeability assays were used to evaluate the change of arsenic concentration, and K562 cell line was applied to evaluate the change of cytotoxicity. The drug concentration-time profiles exhibited that the combination medication group generated higher AUC, t, and longer MRT for arsenic, compared with the single administration of realgar. The apparent permeability coefficients (P) of bidirectional transport in MDCK-MDR1 cell permeability experiments showed that arsenic permeability obviously went up when was incubated together. The combination medication significantly decreased the cell viability of K562 cells when both the concentration of realgar and the concentration of were nontoxic. The pharmacokinetic research, the MDCK-MDR1 based permeability study, and the K562 cytotoxicity study were united together to verify the combination medication of realgar and enhanced the absorption and the permeability across cells for arsenic and effectively inhibited the proliferation of K562 cell line. The molecular binding of AsS and indirubin was analyzed by computational study. It is predicted that the formation of the complex [AsS Indirubin] involves noncovalent interaction that changes the concentration of arsenic.