Transport and uptake characteristics of a new derivative of berberine (CPU-86017) by human intestinal epithelial cell line: Caco-2.
OBJECTIVE
The characteristics of transepithelial transport and uptake of CPU-86017 [[7-(4-chlorbenzyl)-7,8,13,13alpha-tetrahydroberberine chloride, CTHB]], a new antiarrhythmia agent and a new derivative of berberine, were investigated on epithelial cell line (Caco-2) to further understand the absorption mechanism of berberine and its derivatives.


METHODS
Caco-2 cell was used.


RESULTS
1) The permeability coefficient from the apical (AP) to basolateral (BL) of CPU-86017 was approximately 5 times higher than that from BL-to-AP transport. The effects of a P-glycoprotein (P-gp) inhibitor-cyclosporin A, some surfactants, and lower pH on the transepithelial transport of CPU-86017 were also observed. Cyclosporine A at 7.5 mg/L had no effect on the transepithelial electrical resistance (TEER); an about 4-fold enhancement on the transepithlial transport of CPU-86017 was observed. Some surfactants (sodium citrate, sodium deoxycholate, and sodium dodecyl sulfate) at 100 micromol/L and low pH (pH=6.0) induced a reversible decrease of TEER; enhancements of the transepithelial transport of CPU-86017 were also observed with some surfactants; 2) In the process of uptake of CPU-86017, the initial uptake rates of CPU-86017 were saturable with a Vmax of (250+/-39) microg/min/g (protein) and Km of (0.90+/-0.12) mmol/L. This process was enhanced by cyclosporine A (7.5 mg/L) with a Vmax of (588+/-49) microg/min/g (protein) and Km (0.42+/-0.08) mmol/L.


CONCLUSIONS
Some surfactants and P-gp inhibitors can be considered as enhancers of its transepithelial transport and uptake.
Yang
Hai-Tao
HT
Center of Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China. gjwang@mailbox.cpu.edu.cn
Wang
Guang-Ji
GJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D001599:Berberine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002951:Citrates / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D003840:Deoxycholic Acid / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects; D000077559:Sodium Citrate; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology*
C400084:4-chlorobenzyltetrahydroberberine; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002951:Citrates; D013501:Surface-Active Agents; D003840:Deoxycholic Acid; D001599:Berberine; D000077559:Sodium Citrate; D012967:Sodium Dodecyl Sulfate; D016572:Cyclosporine