Aim: 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).
Conclusion: 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.