Effect of St John's wort on the disposition of fexofenadine in the isolated perfused rat liver

J TURKANOVIC, Suong Ngo, R MILNE

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Objectives: This study examined the effects of St John's wort (Hypericum perforatum) on the disposition of fexofenadine, a substrate of P-glycoprotein/organic anion transporting polypeptide, in the isolated perfused rat liver. Methods: Male Sprague-Dawley rats were given St John's wort, 1000 mg/kg, by intragastric gavage once daily for 14 days. On day 15, livers were isolated surgically and perfused in a recirculating system with fexofenadine (2 ?g/ml), either alone or following addition of ciclosporin (0.5 ?g/ml) 5 min before the addition of fexofenadine. Perfusate samples and bile were collected for 60 min. Fexofenadine in perfusate, bile and the homogenised livers was measured by HPLC. Key findings: Administration of St John's wort significantly increased biliary clearance with respect to perfusate and biliary clearance with respect to the concentration in the liver, by 74% and 71%, respectively. This was reversed by ciclosporin. Conclusions: St John's wort enhanced the elimination of fexofenadine into the bile. This could be because it increases the activity of P-glycoprotein on the canalicular membrane of hepatocytes. � 2009 The Authors.
    Original languageEnglish
    Pages (from-to)1037-1042
    Number of pages6
    JournalJournal of Pharmacy and Pharmacology
    Volume61
    Issue number8
    Publication statusPublished - 2009

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    fexofenadine
    Bile
    Liver
    P-Glycoprotein
    Cyclosporine
    Hypericum
    Anions
    Sprague Dawley Rats
    Hepatocytes
    High Pressure Liquid Chromatography
    Peptides

    Cite this

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    title = "Effect of St John's wort on the disposition of fexofenadine in the isolated perfused rat liver",
    abstract = "Objectives: This study examined the effects of St John's wort (Hypericum perforatum) on the disposition of fexofenadine, a substrate of P-glycoprotein/organic anion transporting polypeptide, in the isolated perfused rat liver. Methods: Male Sprague-Dawley rats were given St John's wort, 1000 mg/kg, by intragastric gavage once daily for 14 days. On day 15, livers were isolated surgically and perfused in a recirculating system with fexofenadine (2 ?g/ml), either alone or following addition of ciclosporin (0.5 ?g/ml) 5 min before the addition of fexofenadine. Perfusate samples and bile were collected for 60 min. Fexofenadine in perfusate, bile and the homogenised livers was measured by HPLC. Key findings: Administration of St John's wort significantly increased biliary clearance with respect to perfusate and biliary clearance with respect to the concentration in the liver, by 74{\%} and 71{\%}, respectively. This was reversed by ciclosporin. Conclusions: St John's wort enhanced the elimination of fexofenadine into the bile. This could be because it increases the activity of P-glycoprotein on the canalicular membrane of hepatocytes. � 2009 The Authors.",
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    author = "J TURKANOVIC and Suong Ngo and R MILNE",
    year = "2009",
    language = "English",
    volume = "61",
    pages = "1037--1042",
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    Effect of St John's wort on the disposition of fexofenadine in the isolated perfused rat liver. / TURKANOVIC, J; Ngo, Suong; MILNE, R.

    In: Journal of Pharmacy and Pharmacology, Vol. 61, No. 8, 2009, p. 1037-1042.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Effect of St John's wort on the disposition of fexofenadine in the isolated perfused rat liver

    AU - TURKANOVIC, J

    AU - Ngo, Suong

    AU - MILNE, R

    PY - 2009

    Y1 - 2009

    N2 - Objectives: This study examined the effects of St John's wort (Hypericum perforatum) on the disposition of fexofenadine, a substrate of P-glycoprotein/organic anion transporting polypeptide, in the isolated perfused rat liver. Methods: Male Sprague-Dawley rats were given St John's wort, 1000 mg/kg, by intragastric gavage once daily for 14 days. On day 15, livers were isolated surgically and perfused in a recirculating system with fexofenadine (2 ?g/ml), either alone or following addition of ciclosporin (0.5 ?g/ml) 5 min before the addition of fexofenadine. Perfusate samples and bile were collected for 60 min. Fexofenadine in perfusate, bile and the homogenised livers was measured by HPLC. Key findings: Administration of St John's wort significantly increased biliary clearance with respect to perfusate and biliary clearance with respect to the concentration in the liver, by 74% and 71%, respectively. This was reversed by ciclosporin. Conclusions: St John's wort enhanced the elimination of fexofenadine into the bile. This could be because it increases the activity of P-glycoprotein on the canalicular membrane of hepatocytes. � 2009 The Authors.

    AB - Objectives: This study examined the effects of St John's wort (Hypericum perforatum) on the disposition of fexofenadine, a substrate of P-glycoprotein/organic anion transporting polypeptide, in the isolated perfused rat liver. Methods: Male Sprague-Dawley rats were given St John's wort, 1000 mg/kg, by intragastric gavage once daily for 14 days. On day 15, livers were isolated surgically and perfused in a recirculating system with fexofenadine (2 ?g/ml), either alone or following addition of ciclosporin (0.5 ?g/ml) 5 min before the addition of fexofenadine. Perfusate samples and bile were collected for 60 min. Fexofenadine in perfusate, bile and the homogenised livers was measured by HPLC. Key findings: Administration of St John's wort significantly increased biliary clearance with respect to perfusate and biliary clearance with respect to the concentration in the liver, by 74% and 71%, respectively. This was reversed by ciclosporin. Conclusions: St John's wort enhanced the elimination of fexofenadine into the bile. This could be because it increases the activity of P-glycoprotein on the canalicular membrane of hepatocytes. � 2009 The Authors.

    KW - cyclosporin A

    KW - fexofenadine

    KW - Hypericum perforatum extract

    KW - cyclosporin

    KW - drug derivative

    KW - glycoprotein P

    KW - histamine H1 receptor antagonist

    KW - plant extract

    KW - terfenadine

    KW - animal experiment

    KW - animal tissue

    KW - area under the curve

    KW - article

    KW - biliary excretion

    KW - controlled study

    KW - drug absorption

    KW - drug bile level

    KW - drug clearance

    KW - drug disposition

    KW - drug potentiation

    KW - high performance liquid chromatography

    KW - isolated liver

    KW - liver homogenate

    KW - liver perfusion

    KW - male

    KW - nonhuman

    KW - rat

    KW - animal

    KW - chemistry

    KW - drug effect

    KW - drug interaction

    KW - Hypericum

    KW - liver

    KW - liver cell

    KW - metabolism

    KW - Sprague Dawley rat

    KW - Animals

    KW - Chromatography, High Pressure Liquid

    KW - Cyclosporine

    KW - Drug Interactions

    KW - Hepatocytes

    KW - Histamine H1 Antagonists, Non-Sedating

    KW - Liver

    KW - Male

    KW - P-Glycoprotein

    KW - Plant Extracts

    KW - Rats

    KW - Rats, Sprague-Dawley

    KW - Terfenadine

    M3 - Article

    VL - 61

    SP - 1037

    EP - 1042

    JO - Journal of Pharmacy and Pharmacology

    JF - Journal of Pharmacy and Pharmacology

    SN - 0022-3573

    IS - 8

    ER -