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- Title
PIII-63.
- Authors
Zhu, H. J.; Wang, J. S.; Markowitz, J. S.; Donovan, J. L.; Gibson, B. B.; Gefroh, H. A.; DeVane, L. C.
- Abstract
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 IC50 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 Papp 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
- Subjects
CANNABINOIDS; ADENOSINE triphosphatase; DOXORUBICIN; MARIJUANA; BIOLOGICAL transport
- Publication
Clinical Pharmacology & Therapeutics, 2006, Vol 79, Issue 2, pP75
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1016/j.clpt.2005.12.271