Grapefruit juice effects on the bioavailability of cyclosporin-A in rats
Previous studies indicate that blood levels of cyclosporin-A are increased by concomittant administration of grapefruit juice in healthy subjects and patients. It was suggested that grapefruit juice could inhibit the metabolism of cyclosporin-A by CYP3A4, the predominant cytochrome P450 enzyme in the gut wall and liver. However, up to date, the mechanism of action of grapefruit juice has not been conclusively identified and no work has been conducted in animals to quantify its effect on cyclosporin-A metabolism. This study compared the disposition of cyclosporin-A (5 mg/kg) coadministered with grapefruit juice, orange juice or water (10 ml/kg) in male Sprague-Dawley rats. Time to peak concentration was about 5 h for each group. Area under the blood concentration-time curve and peak concentration of cyclosporin-A were increased by 31% and 20%, respectively, with grapefruit juice (P < 0.05). The effects of grapefruit juice were not duplicated by orange juice which did not differ significantly from water for any of the parameters tested. These results confirm that grapefruit juice may act as an inhibitor of drug metabolism altering the disposition of concomittantly administered cyclosporin-A in rats. Nonetheless, it was demonstrated that, under appropriate experimental conditions, rats may be suitable models for in vivo investigation of the interaction mechanism between grapefruit juice and cyclosporin-A.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2001 |
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| Erschienen: |
2001 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
European review for medical and pharmacological sciences - 5(2001), 1 vom: 18. Jan., Seite 1-6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mangano, N G [VerfasserIn] |
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| Themen: |
83HN0GTJ6D |
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| Anmerkungen: |
Date Completed 01.04.2002 Date Revised 21.11.2013 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM117457019 |
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| 100 | 1 | |a Mangano, N G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Grapefruit juice effects on the bioavailability of cyclosporin-A in rats |
| 264 | 1 | |c 2001 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 01.04.2002 | ||
| 500 | |a Date Revised 21.11.2013 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Previous studies indicate that blood levels of cyclosporin-A are increased by concomittant administration of grapefruit juice in healthy subjects and patients. It was suggested that grapefruit juice could inhibit the metabolism of cyclosporin-A by CYP3A4, the predominant cytochrome P450 enzyme in the gut wall and liver. However, up to date, the mechanism of action of grapefruit juice has not been conclusively identified and no work has been conducted in animals to quantify its effect on cyclosporin-A metabolism. This study compared the disposition of cyclosporin-A (5 mg/kg) coadministered with grapefruit juice, orange juice or water (10 ml/kg) in male Sprague-Dawley rats. Time to peak concentration was about 5 h for each group. Area under the blood concentration-time curve and peak concentration of cyclosporin-A were increased by 31% and 20%, respectively, with grapefruit juice (P < 0.05). The effects of grapefruit juice were not duplicated by orange juice which did not differ significantly from water for any of the parameters tested. These results confirm that grapefruit juice may act as an inhibitor of drug metabolism altering the disposition of concomittantly administered cyclosporin-A in rats. Nonetheless, it was demonstrated that, under appropriate experimental conditions, rats may be suitable models for in vivo investigation of the interaction mechanism between grapefruit juice and cyclosporin-A | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Cyclosporine |2 NLM | |
| 650 | 7 | |a 83HN0GTJ6D |2 NLM | |
| 700 | 1 | |a Cutuli, V M |e verfasserin |4 aut | |
| 700 | 1 | |a Caruso, A |e verfasserin |4 aut | |
| 700 | 1 | |a De Bernardis, E |e verfasserin |4 aut | |
| 700 | 1 | |a Amico-Roxas, M |e verfasserin |4 aut | |
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