Apricot extract inhibits the P-gp-mediated efflux of talinolol.
Within the framework of developing strategies to enhance the intestinal absorption of P-glycoprotein (P-gp) substrates, the modulatory effect of a standardized apricot extract on P-gp-related efflux carriers was investigated in the Caco-2 system, Ussing chambers and the rat in situ perfusion model using talinolol as a model substrate. Using the Caco-2 system, polarity in transport of talinolol could be observed, the absorptive transport being much lower than the secretory transport (P(app-abs) = 1.08 +/- 0.29 x 10(-6) cm/s and P(app-secr) = 11.74 +/- 0.80 x 10(-6) cm/s). Inclusion of apricot extract (1%) in the apical medium resulted in a statistically significantly diminished polarity (P(app-abs) = 4.88 +/- 0.96 x 10(-6) cm/s and P(app-secr) = 9.39 +/- 0.58 x 10(-6) cm/s, p < 0.05). In addition, the inhibitory effect of apricot extract on P-gp related efflux mechanisms was shown to be concentration (0% approximately 0.1% < 0.3% < 1%) and pH dependent. Experiments performed with the Ussing chambers resulted in similar observations. In the rat in situ perfusion model, inclusion of apricot extract (1%) in the perfusion medium resulted in a threefold increase of the amount of talinolol appearing in the collected blood compared to the reference condition (23.6 +/- 5.53 pmol/cm. min and 7.13 +/- 1.08 pmol/cm. min, respectively; p < 0.05). Coadministration of this standardized apricot extract might be a safe and useful strategy to enhance the intestinal absorption of P-gp substrates. The nature and structure of the compound(s) responsible for this inhibiting effect on P-gp-related efflux carriers remain to be elucidated, as well as the exact mechanism by which apricot extract exerts its inhibitory function.
Deferme
Sven
S
Laboratory for Pharmacotechnology and Biopharmacy, Herestraat 49, Gasthuisberg, 3000 Leuven, Belgium.
Mols
Raf
R
Van Driessche
Willy
W
Augustijns
Patrick
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D000818:Animals; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D008297:Male; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000494:pharmacology*; D011412:Propanolamines / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D027861:Prunus; D051381:Rats; D017208:Rats, Wistar
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010936:Plant Extracts; D011412:Propanolamines; C011550:talinolol