An investigation on intestinal absorption of a new anticancer drug, 2-methoxyestradiol.
In this paper, the intestinal absorptive property of a new anticancer drug, 2-methoxyestradiol (2ME2) was investigated by in situ rat intestinal recirculation perfusion experimental techniques. The results indicated that the concentrations of 2ME2 had no influence on absorption rate constant (ka) of 2ME2 and the small intestinal absorption of 2ME2 was a first-order process with passive diffusion mechanism within the concentration tested. 2ME2 was well absorbed at each intestinal segment except duodenum and the best site of intestinal absorption of 2ME2 was the ileum. In addition, the PH of drug perfusate and the concentration of SDS had significant effects on absorption kinetics. Faintly basic environment profitted small intestinal absorption of 2ME2. Tween 80 and SDS could not enhance the intestinal absorption of 2ME2. The above study provided a theoretical foundation for developing effective oral preparations with higher bioavailability to treat cancers. In addition, the improved ligation way for studying the best site of intestinal absorption of 2ME2, should be used extensively in related studies because of decreasing number of experimental rats and saving time.
Guo
Xin-Hong
XH
School of Pharmacy, Zhengzhou University, China.
Zhang
Nan
N
Cui
Fu-De
FD
Du
Bin
B
Zhang
Zhen-Zhong
ZZ
D000077584:2-Methoxyestradiol; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004121:Dimethyl Sulfoxide; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D051381:Rats; D012995:Solubility; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents / Q000737:chemistry
D018931:Antineoplastic Agents, Hormonal; D012997:Solvents; D013501:Surface-Active Agents; D004958:Estradiol; D000077584:2-Methoxyestradiol; D004121:Dimethyl Sulfoxide