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Evidence of reduced oral bioavailability of paracetamol in rats following multiple ingestion of grapefruit juice

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Abstract

The aim of the current investigation was to assess the ability GFJ to modulate the pharmacokinetic profile of paracetamol following single or repeated administrations of GFJ in Sprague–Dawley rats. Diclofenac and carbamazepine were both used as positive controls. Rats received single GFJ or single distilled water doses or pretreated with three doses of GFJ prior to test drug administration. Blood samples were collected, processed and analyzed using validated HPLC methods, and pharmacokinetic data were constructed for each group. Increase in the bioavailability of both diclofenac and carbamazepine following multiple GFJ ingestion was revealed. Conversely, the bioavailability of paracetamol was significantly reduced following multiple GFJ administration. The percentage of reduction in the C max and AUC of paracetamol were calculated as 31 and 51 %, respectively, compared to none-GFJ-treated control (P < 0.05). The T max was not essentially changed. In conclusion, frequent administration of GFJ was confirmed to modulate the pharmacokinetics of paracetamol in rats by reducing its bioavailability. Meanwhile, it may be advisable not to ingest large amounts of GFJ along with paracetamol to avoid a possible potential loss of the efficacy.

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Acknowledgments

This work was funded by the Deanship of Scientific Research, University of Petra, Amman, Jordan.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. 961343, Amman, 11196, Jordan

    Nidal A. Qinna, Obbei A. Ismail & Tawfiq M. Alhussainy

  2. Department of Pharmaceutics and Pharmaceutical Technology, University of Petra, P.O. 961343, Amman, 11196, Jordan

    Nasir M. Idkaidek

  3. Department of Pharmaceutical Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman, Jordan

    Tawfiq A. Arafat

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  1. Nidal A. Qinna
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  2. Obbei A. Ismail
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  5. Tawfiq A. Arafat
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Correspondence to Nidal A. Qinna.

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Qinna, N.A., Ismail, O.A., Alhussainy, T.M. et al. Evidence of reduced oral bioavailability of paracetamol in rats following multiple ingestion of grapefruit juice. Eur J Drug Metab Pharmacokinet 41, 187–195 (2016). https://doi.org/10.1007/s13318-014-0251-4

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  • DOI: https://doi.org/10.1007/s13318-014-0251-4

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