Effects ofNigella sativaandLepidium sativumon Cyclosporine Pharmacokinetics

Abstract

The present study was conducted to investigate the effects of Nigella sativa and Lepidium sativum on the pharmacokinetics of cyclosporine in rabbits. Two groups of animals were treated separately with Nigella sativa (200 mg/kg p.o.) or Lepidium sativum (150 mg/kg p.o.) for eight consecutive days. On the 8th day, cyclosporine (30 mg/kg p.o.) was administered to each group one hour after herbal treatment. Blood samples were withdrawn at different time intervals (0.0, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, and 24 hrs) from marginal ear vein. Cyclosporine was analyzed using UPLC/MS method. The coadministration of Nigella sativa significantly decreased the C max and AUC0−∞ of cyclosporine; the change was observed by 35.5% and 55.9%, respectively (P ≤ 0.05). Lepidium sativum did not produce any significant change in C max of cyclosporine, although its absorption was significantly delayed compared with control group. A remarkable change was observed in T max and AUC0−t of Lepidium sativum treated group. Our findings suggest that concurrent consumption of Nigella sativa and Lepidium sativum could alter the pharmacokinetics of cyclosporine at various levels.

Herbal Bioenhancers in Veterinary Phytomedicine

“…Besides improving the intestinal permeability, the fatty acids of black cumin (especially eicosadeinoic acid) were found to inhibit the P-gp activity in silico against the primary amino acid sequence of P-gp from rats leading increased bioavailability of drugs ( 56 ). Contrary to in silico analysis, black cumin is associated with the activation of intestinal P-gp and/or CYP3A4, due to its ability to decrease the bioavailability of cyclosporine (cyclic polypeptide used as immunosuppressant in organ transplantation) in coadministration ( 57 ). Black cumin induced no significant effect on the theophylline pharmakokinetics in Beagle dogs indicating its lack of affinity to CYP1A2 activity; meanwhile fenugreek and garden cress decreased the bioavailability ( 58 ).…”

Inhibition of cytochrome P450 enzymes by thymoquinone in human liver microsomes

“…A similar study, using tolbutamide as a substrate, showed that its oil extract had considerable inhibitory effects against CYP2C11 (Korashy et al 2015). However, when N. sativa was co-administered with cyclosporine in an animal model, the oral bioavailability of cyclosporine was significantly reduced, suggesting the possibility that N. sativa induced intestinal P-glycoprotein and/or hepatic CYP3A activity (Al-Jenoobi et al 2013). Another study presented that the dietary dose of TQ substantially modulate the activity of hepatic xenobiotic metabolizing enzyme in rabbits (Elbarbry et al 2012).…”

Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism

“…In that study, the C max and AUC 0−∞ of cyclosporine (30 mg/kg) significantly decreased by 35.5% and 55.9%, respectively, after pretreatment with Nigella (200 mg/kg). However, a significant increase in cyclosporine clearance (~2-fold) was observed, thus suggesting that intestinal P-gp and/or CYP3A4 are activated in the presence of N. sativa [144].…”