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Carbamazepine is not a substrate for P-glycoprotein
A Owen1, M Pirmohamed, J N Tettey
1Department of Pharmacology and Therapeutics, The University of Liverpool, L69 3GE, UK.
British Journal of Clinical Pharmacology
|April 25, 2001
Summary
Carbamazepine (CBZ) does not appear to be a substrate for P-glycoprotein (Pgp). This suggests that Pgp over-expression in the brain is unlikely to affect CBZ
Area of Science:
- Pharmacology
- Drug Transport
- Biochemistry
Background:
- Carbamazepine (CBZ) is an anticonvulsant drug.
- CYP3A4 is a key enzyme in drug metabolism.
- P-glycoprotein (Pgp) is a multidrug efflux transporter involved in drug distribution.
Purpose of the Study:
- To investigate if carbamazepine (CBZ) is a substrate for P-glycoprotein (Pgp).
- To assess the role of Pgp in the brain penetration and intestinal absorption of CBZ.
- To clarify the interaction of CBZ with Pgp and CYP3A4.
Main Methods:
- Assessed CBZ brain penetration in mdr1a/1b(-/-) and wild-type mice.
- Evaluated CBZ transport across Caco-2 cell monolayers.
- Used flow cytometry with rhodamine 123 in lymphocytes to assess Pgp activity.
Main Results:
- Brain penetration of CBZ was similar in both mouse models.
- CBZ transport in Caco-2 cells was independent of Pgp and unaffected by a Pgp inhibitor.
- CBZ did not affect rhodamine 123 efflux from lymphocytes, unlike verapamil.
Conclusions:
- Carbamazepine (CBZ) is not a substrate for P-glycoprotein (Pgp).
- Pgp over-expression in the brain is unlikely to impact CBZ efficacy.
- Interactions between CBZ and drugs like verapamil likely involve CYP3A4 inhibition, not Pgp modulation.