**6.5** *Nigella sativa* **pharmacokinetics**

One of the main active constituents in *N. sativa* seeds and oil is thymoquinone. Thymoquinone has shown to bind to human α(1)-acid glycoprotein in the plasma [111] and inhibit CYP2C9 > 2D6 > 1A2 > 3A4 liver enzymes [112]. In hypertensive rats, *N. sativa* + alompidine showed greater reduction in blood pressure and heart rate than *N. sativa* alone, but no effect on alompidine pharmacokinetics (Cmax, AUC0-t, Kel, and terminal half-life) [113]. In another study in hypertensive rats, *N. sativa* + losartan showed greater reduction in blood pressure than *N. sativa* alone. *N. sativa* slightly reduced losartan Cmax and AUC0-t [114]. Alompidine is metabolized by CYP3A4 and losartan by CYP2C9 and 3A4 in humans. These data suggest that *N. sativa* has minimal effect on CYP3A4 but inhibits CYP2C9. In other words, *N. sativa* has antihypertensive effects on its own but potentiates the effect of drugs metabolized by CYP2C9 which can cause further drop in blood pressure and lead to side effects such as fainting.

### **6.6** *Nigella sativa* **safety summary**

*N. sativa* whole seeds, oil or polar extracts (i.e., non-aqueous) at human doses up to 3 g/day for 12 weeks beneficially affect inflammatory and metabolic markers without adverse effects on heart, liver, or kidneys in healthy adults as well as in patients with heart disease and diabetes. *N. sativa* reduces blood glucose and blood pressure. Thus, caution when combining with hypoglycemic and antihypertensive drugs to avoid side effects. *N. sativa* can increase the bioavailability of

*Safety Review of Herbs and Supplements in Heart Disease, Diabetes, and COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.96811*

drugs metabolized by CYP2C9 leading to higher risks of their side effects. Some diabetes and heart medications metabolized by CYP2C9 are losartan, fluvastatin, glipizide [25].
