Qinna Nidal A, Ismail Obbei A, Alhussainy Tawfiq M, Idkaidek Nasir M, Arafat Tawfiq A
Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. 961343, Amman, 11196, Jordan.
Department of Pharmaceutics and Pharmaceutical Technology, University of Petra, P.O. 961343, Amman, 11196, Jordan.
Eur J Drug Metab Pharmacokinet. 2016 Apr;41(2):187-95. doi: 10.1007/s13318-014-0251-4. Epub 2014 Dec 30.
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.
当前研究的目的是评估在斯普拉格-道利大鼠单次或重复给予GFJ后，GFJ调节对乙酰氨基酚药代动力学特征的能力。双氯芬酸和卡马西平均用作阳性对照。大鼠接受单次GFJ或单次蒸馏水剂量，或在给予受试药物前用三剂GFJ进行预处理。采集血样，采用经过验证的高效液相色谱法进行处理和分析，并为每组构建药代动力学数据。结果显示，多次摄入GFJ后双氯芬酸和卡马西平的生物利用度均有所增加。相反，多次给予GFJ后对乙酰氨基酚的生物利用度显著降低。与未用GFJ处理的对照组相比，对乙酰氨基酚Cmax和AUC的降低百分比分别计算为31%和51%（P<0.05）。T(max)基本未发生变化。总之，证实频繁给予GFJ可通过降低对乙酰氨基酚的生物利用度来调节其在大鼠体内的药代动力学。同时，建议不要将大量GFJ与对乙酰氨基酚一起摄入，以避免可能的疗效潜在损失。
