Al-Jenoobi Fahad I, Alam Mohd Aftab, Alkharfy Khalid M, Al-Suwayeh Saleh A, Korashy Hesham M, Al-Mohizea Abdullah M, Iqbal Muzaffar, Ahad Abdul, Raish Mohammad
Eur J Drug Metab Pharmacokinet. 2014 Jun;39(2):147-53. doi: 10.1007/s13318-013-0149-6.
The present study investigated the effect of fenugreek seed powder on disposition of CYP3A substrates, cyclosporine and carbamazepine. Rabbits were treated with fenugreek seed powder (300 mg/kg p.o.) for 8 days and on 8th day the single dose of cyclosporine (30 mg/kg, p.o.) and carbamazepine (40 mg/kg, p.o.) were administered to the corresponding group after 1 h of fenugreek administration. Blood samples were drawn at several time points and analyzed by using UPLC-MS (cyclosporine) and HPLC (carbamazepine). Pharmacokinetic parameters were calculated by using PK Solver. The present investigation reveals that there was no statistically significant difference between pre- and post-treated pharmacokinetic parameters such as AUC(o-t), AUC(o-∞), C(max), T(max), T(1/2), K(el), MRT(o-∞) , V(z/F), and Cl/F for cyclosporine and carbamazepine. Two tailed "P" values for all these pharmacokinetic parameters were more than 0.05, indicating insignificant impact of fenugreek treatment on the disposition of cyclosporine and carbamazepine. Further, fenugreek may also not have any significant effect on the functionality of P-glycoprotein as cyclosporine is a substrate to P-glycoprotein. The outcomes of present study suggested that fenugreek may not likely to interfere cyclosporine and carbamazepine pharmacokinetics, when co-administered with these drugs.
本研究调查了胡芦巴籽粉对细胞色素P450 3A（CYP3A）底物环孢素和卡马西平处置的影响。用胡芦巴籽粉（300毫克/千克，口服）对兔子进行治疗，持续8天，在第8天，在给予胡芦巴1小时后，对相应组分别单次给予环孢素（30毫克/千克，口服）和卡马西平（40毫克/千克，口服）。在多个时间点采集血样，并使用超高效液相色谱-质谱联用仪（用于环孢素）和高效液相色谱仪（用于卡马西平）进行分析。使用PK Solver计算药代动力学参数。本研究表明，环孢素和卡马西平治疗前和治疗后的药代动力学参数，如药时曲线下面积（AUC(o-t)）、药时曲线下总面积（AUC(o-∞)）、血药浓度峰值（C(max)）、达峰时间（T(max)）、半衰期（T(1/2)）、消除速率常数（K(el)）、平均滞留时间（MRT(o-∞)）、表观分布容积（V(z/F)）和清除率（Cl/F），在统计学上没有显著差异。所有这些药代动力学参数的双侧“P”值均大于0.05，表明胡芦巴治疗对环孢素和卡马西平的处置影响不显著。此外，由于环孢素是P-糖蛋白的底物，胡芦巴可能对P-糖蛋白的功能也没有任何显著影响。本研究结果表明，胡芦巴与这些药物合用时，不太可能干扰环孢素和卡马西平的药代动力学。
