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PIII‐63
Author(s) -
Zhu H. J.,
Wang J. S.,
Markowitz J. S.,
Donovan J. L.,
Gibson B. B.,
Gefroh H. A.,
DeVane L. C.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.271
Subject(s) - cannabidiol , p glycoprotein , verapamil , chemistry , rhodamine 123 , pharmacology , cannabinoid , ic50 , atpase , efflux , in vitro , biochemistry , biology , medicine , enzyme , multiple drug resistance , calcium , receptor , cannabis , organic chemistry , psychiatry , antibiotics
AIMS The purpose of this study was to investigate the possible interaction of P‐gp and each of four major marijuana constituents (THC, THC‐COOH, CBN and CBD). METHODS ATPase activity assay was conducted for measuring the cannabinoids binding affinity for P‐gp. LLC‐PK1/MDR1 cells and caco‐2 cells were used to evaluate the effect of CBD on the uptake of P‐gp substrates rhodamine 123 (Rh123) and doxorubicin (DOX). The effects of CBD on the transport of Rh123 across caco‐2 and primary cultured rat brain microvessels cells (RBMECs) monolayers were studied in both the basal to apical (B‐A) and the apical to basal (A‐B) directions. RESULTS The data of the P‐gp ATPase showed that all four cannabinoids stimulated P‐gp ATPase activity. Furthermore, CBD showed a concentration‐dependent inhibitory effect on the verapamil stimulated ATPase activity with an IC 50 value of 39.6μM. At concentrations ranging from 5μM to 100μM, CBD robustly enhanced the intracellular accumulation of Rh123 and DOX. Following exposure to CBD, the transport rate of Rh123 was significantly decreased in B‐A directions, but increased in A‐B directions. Compared with the control group, the ratios of P app of B‐A and A‐B directions were dramatically decreased in both caco‐2 and RBMECs cells in the presence of 30μM of CBD. CONCLUSION These findings indicate that CBD inhibits P‐gp‐mediated drug transport, suggesting CBD could potentially influence the absorption and disposition of other coadministered compounds that are P‐gp substrates. Clinical Pharmacology & Therapeutics (2005) 79 , P75–P75; doi: 10.1016/j.clpt.2005.12.271