These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The intestinal absorption of camptothecin, a highly lipophilic drug, across Caco-2 cells is mediated by active transporter(s).
    Author: Gupta E, Luo F, Lallo A, Ramanathan S, Vyas V, Rubin E, Sinko P.
    Journal: Anticancer Res; 2000; 20(2A):1013-6. PubMed ID: 10810389.
    Abstract:
    The intestinal transport properties and kinetics of camptothecin (CPT) through Caco-2 cell monolayers were characterized by determining concentration-, temperature-, and ATP-dependence as well as the effect of selected inhibitors. The absorptive permeability (Peff) of CPT was found to be concentration dependent and saturable (K(m) = 31.2 +/- 6.9 microM) indicating the involvement of a high affinity, low capacity transport system. CPT transport was also temperature dependent and inhibited by sodium azide plus 2-deoxyglucose, which deplete cellular ATP, further suggesting that an active, carrier-mediated transport system contributes to CPT absorption. Based on inhibition studies, the involvement of organic anion and cation transporters was implicated but not conclusively demonstrated. Total CPT transport decreased four fold with increasing pH from 5.5 to 8.5 indicating that CPT lactone contributed more significantly to overall CPT transport than CPT carboxylate. The results of these studies suggest that CPT absorption is mediated by multiple mechanisms including significant passive diffusion and active transport components. Since typical substrates for intestinal carriers are hydrophilic and charged, the involvement of putative absorptive carriers in the transport of CPT is a novel finding that may give insight into the erratic oral bioavailability of CPTs observed in the clinic.
    [Abstract] [Full Text] [Related] [New Search]