Pharmacokinetic interaction studies of fenugreek with CYP3A substrates cyclosporine and carbamazepine

Abstract

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.

Nigella sativa and Trigonella foenum-graecum Supplemented Chapatis Safely Improve HbA1c, Body Weight, Waist Circumference, Blood Lipids, and Fatty Liver in Overweight and Diabetic Subjects: A Twelve-Week Safety and Efficacy Study

“…Consistent with published clinical data regarding N. sativa and fenugreek in combination or alone, the consumption of NFC had no adverse effect on hepatic, kidney, or thyroid functioning. 15 , 28 , 60 , 61 While in vitro and animal studies describe the potential for an interaction of N. sativa or fenugreek phytoceuticals with drugs metabolized by hepatic CYP3A4, 62 , 63 in our study one subject receiving metoprolol (a CYP3A4 substrate) therapy for hypertension maintained readings of 120, 80, 40, and 93 mmHg for SBP, DBP, PP, and MAP, respectively, from baseline through 12 weeks.…”

Potential pharmacodynamic and pharmacokinetic interactions of Nigella Sativa and Trigonella Foenum-graecum with losartan in L-NAME induced hypertensive rats

“…Earlier studies have described that herbs like N. Sativa and T. Foenum-graecum possibly will inhibit the activity of CYP3A ( Albassam et al, 2018 , Al-Jenoobi et al, 2014a , Al-Jenoobi et al, 2014b , Alkharfy et al, 2013 , Korashy et al, 2015 ). The losartan in general metabolized by CYP3A4 and CYP2C9, and hence, we proposed that the herb-losartan interaction could happen owing to the effects of investigated herbs on the activity of these enzymes.…”

“…The prepared aqueous saline suspension of each herb was then sonicated for 10–15 min. The calculated volume of suspension was then administered to rats as per their body weight with the help rats oral feeding needle and syringe ( Al-Jenoobi et al, 2014a , Al-Jenoobi et al, 2014b , Korashy et al, 2015 ).…”

“…Group 2 rats were received L-NAME + N. Sativa (300 mg/kg) ( Al-Jenoobi et al, 2014b , Korashy et al, 2015 ) for 2 weeks and on 14th day, systolic blood pressure of each rat was measured at 0, 1, 2, 4, 8 and 12 h and on 15th day, losartan (10 mg/kg, orally) was given as single dose and systolic blood pressure was monitored 0, 1, 2, 4, 8 and 12 h. Three days later (washout period), losartan (10 mg/kg, orally) was again given as single dose and blood samples were taken out from the rats at 0, 0.5, 1, 2, 4, 8 and 12 h and plasma samples were detected for drug content by UPLC-MS-MS method ( Alam et al, 2019 ). Similarly, in Group 3, animals were received L-NAME + T. Foenum-graecum (300 mg/kg) ( Al-Jenoobi et al, 2014a , Al-Jenoobi et al, 2014b , Korashy et al, 2015 ) for 2 weeks and on 14th day, systolic blood pressure of each rat was measured at 0, 1, 2, 4, 8 and 12 h and on 15th day, losartan (10 mg/kg, orally) was given as single dose and systolic blood pressure was monitored at 0, 1, 2, 4, 8 and 12 h. After three days of washout period, losartan (10 mg/kg, orally) again given as single dose and blood samples were taken out from the animals at 0, 0.5, 1, 2, 4, 8 and 12 h and biological samples were evaluated for losartan content by UPLC-MS-MS method ( Alam et al, 2019 ).…”