[The in vitro kinetics of uptake, transport and efflux of 9-nitrocamptothecin in Caco-2 cell model].
OBJECTIVE
To study the kinetics of uptake, transepithelial transport and efflux of 9-nitrocamptothecin (9-NC).


METHODS
A human intestinal epithelial cell model Caco-2 cell in vitro cultured had been applied to study the kinetics of uptake, transport and efflux kinetics of 9-NC at small intestine. The effects of time, pH, temperature and P-glycoprotein inhibitors on the uptake of 9-NC were investigated. The determination of 9-NC was performed by HPLC.


RESULTS
The uptake and absorption of 9-NC were passive diffusion as the dominating process. The uptake of 9-NC is positively correlated to uptake time, and negatively correlated to pH and temperature. The inhibitors, cyclosporine A and verapamil, significantly enhanced the uptake amount of 9-NC (P < 0.05). P(app) of Basolateral to Apical was much more than that of Apical to Basolateral (2.6-6.9 fold). The efflux of 9-NC was fitted to apparent two-order process. The m0 [(148.0 +/- 2.2) pmol x cm(-2)] and the efflux rate (41.1 pmol x cm2 min(-1)) on Apical side were higher than the m0 [(121 +/- 7) pmol x cm(-2)] (P < 0.05) and the efflux rate (29.2 pmol x cm2 x min(-1)) on Basolateral side (P < 0.01).


CONCLUSIONS
The uptake and absorption of 9-NC were passive diffusion as the dominating process. P-glycoprotein had strong efflux effects on the uptake and transepithelial transport of 9-NC.
Sha
Xian-yi
XY
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Fang
Xiao-ling
XL
Wu
Yun-juan
YJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001692:Biological Transport; D018938:Caco-2 Cells / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013696:Temperature; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D016572:Cyclosporine; D014700:Verapamil; C079905:rubitecan; D002166:Camptothecin