Talinolol-verapamil interaction is not solely due to P-glycoprotein inhibition

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Abstract

Recent studies suggest that disposition of talinolol (TAL) is affected by the efflux pump, P-glycoprotein (P-gp). However, co-administration of verapamil (VER), a known P-gp inhibitor, and TAL in humans resulted in decreased TAL plasma levels instead of a predicted increase resulting from VER-mediated inhibition of intestinal P-gp. In the current study, we show that TAL is actively transported across polarized epithelial cells expressing high levels of P-gp (LMDR1). Moreover, when TAL was orally administered to mice, plasma levels were nearly 3-fold higher in the mdr1a/1b-deficient (-/-) mice, compared to their wildtype (+/+) counterpart. However, co-administration of TAL (16 mg.kg-1) to (+/+) and (-/-) mice resulted in a significant reduction in TAL plasma levels (ng.ml-1 at 1 hr, mean±SD) in both groups: TAL TAL+VER (+/+) 361±155 96±77 (-/-) 1054±349 575±283 These findings suggest that inhibition by VER of a TAL intestinal uptake transport system(s) may overshadow the effects of VER on P-gp.

Details

Original languageEnglish
Pages (from-to)P85
JournalClinical Pharmacology and Therapeutics
Volume69
Issue number2
Publication statusPublished - 2001
Peer-reviewedYes

External IDs

ORCID /0000-0003-1526-997X/work/142247258

Keywords

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