Pre-clinical evidence of enhanced oral bioavailability of the P-glycoprotein substrate talinolol in combination with morin

Shriram M. Pathak, N. Udupa

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 5.0mgkg -1), on the pharmacokinetics of orally (10mgkg-1) and intravenously (1.0mgkg-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 5.0mgkg-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.

Original languageEnglish
Pages (from-to)202-214
Number of pages13
JournalBiopharmaceutics and Drug Disposition
Volume31
Issue number2-3
DOIs
Publication statusPublished - 2010

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talinolol
P-Glycoprotein
Biological Availability
Pharmacokinetics
Pharmaceutical Preparations
morin
Ileum
Flavonoids

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

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title = "Pre-clinical evidence of enhanced oral bioavailability of the P-glycoprotein substrate talinolol in combination with morin",
abstract = "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 5.0mgkg -1), on the pharmacokinetics of orally (10mgkg-1) and intravenously (1.0mgkg-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 5.0mgkg-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.",
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Pre-clinical evidence of enhanced oral bioavailability of the P-glycoprotein substrate talinolol in combination with morin. / Pathak, Shriram M.; Udupa, N.

In: Biopharmaceutics and Drug Disposition, Vol. 31, No. 2-3, 2010, p. 202-214.

Research output: Contribution to journalArticle

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