title: Evidence of reduced oral bioavailability of paracetamol in rats following multiple ingestion of grapefruit juice.
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.
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. 961343, Amman, 11196, Jordan. nqinna@uop.edu.jo.
authors.forename: Nidal A
authors.initials: NA
authors.lastname: Qinna
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. 961343, Amman, 11196, Jordan.
authors.forename: Obbei A
authors.initials: OA
authors.lastname: Ismail
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. 961343, Amman, 11196, Jordan.
authors.forename: Tawfiq M
authors.initials: TM
authors.lastname: Alhussainy
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, University of Petra, P.O. 961343, Amman, 11196, Jordan.
authors.forename: Nasir M
authors.initials: NM
authors.lastname: Idkaidek
authors.affiliation: Department of Pharmaceutical Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman, Jordan.
authors.forename: Tawfiq A
authors.initials: TA
authors.lastname: Arafat
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001628:Beverages / Q000009:adverse effects*; D001682:Biological Availability; D002220:Carbamazepine / Q000493:pharmacokinetics; D032083:Citrus paradisi / Q000009:adverse effects*; D004008:Diclofenac / Q000493:pharmacokinetics; D004435:Eating; D018565:Food-Drug Interactions; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004008:Diclofenac; D002220:Carbamazepine; D000082:Acetaminophen
keywords: Acetaminophen; Anion-transporting polypeptide; Carbamazepine; Cytochrome P450; Diclofenac; Drug–food interactions; P-glycoprotein