Pre-clinical evidence of enhanced oral bioavailability of the P-glycoprotein substrate talinolol in combination with morin.
Most known interactions between herbal extracts and drugs involve the inhibition of drug-metabolizing enzymes, but little is yet known about the possible role of transporters in these interactions. In order to evaluate the effect of one of such prominent flavonoids, morin, on P-glycoprotein related efflux carriers, measurements of transport characteristics through Ussing chambers, in situ perfusion and in vivo drug absorption studies were performed with the transported, yet not metabolized model compound talinolol.This study investigated the effects of orally administered morin (1.0, 2.5 and 5.0 mg kg(-1)), on the pharmacokinetics of orally (10 mg kg(-1)) and intravenously (1.0 mg kg(-1)) administered talinolol in rats. In the presence of morin, the pharmacokinetic parameters of talinolol were significantly altered in the oral group but not in the intravenous group. The presence of 2.5 and 5.0 mg kg(-1) of morin significantly increased (1.8-2.0 fold, p<0.01) the area under the plasma concentration-time curve and the peak plasma concentration (2.3-3.0 fold, p<0.01) of orally administered talinolol. The absolute bioavailability (F %) of talinolol in the rats pretreated with morin was significantly higher (89.09-98.29%, p<0.01) than the control (52.14%). Talinolol demonstrated asymmetric transport across rat ileum with significantly greater basolateral-to-apical (B-A) permeability than that in the apical-to-basolateral (A-B) direction. The addition of morin resulted in a concentration dependent effect, especially on the secretory transport of talinolol.The present study demonstrates that morin bears the ability to interfere with secretory intestinal transport processes. This might be due to an interaction with P-glycoprotein.
Pathak
Shriram M
SM
Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal-University, Manipal-576104, Karnataka, India. shriram.pathak@manipal.edu
Udupa
N
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics; D001682:Biological Availability; D018938:Caco-2 Cells; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D004347:Drug Interactions / Q000502:physiology; D005419:Flavonoids / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D011412:Propanolamines / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D047309:Flavones
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000959:Antihypertensive Agents; D000972:Antineoplastic Agents, Phytogenic; D002121:Calcium Channel Blockers; D005419:Flavonoids; D011412:Propanolamines; C011550:talinolol; C008548:morin; D047309:Flavones