Carbamazepine Shows Plasma and Tissue Pharmacokinetic Interactions with Ajuga bracteosa Extract in Rats

Abstract Carbamazepine (CBZ) is the first-line anticonvulsant drug with a narrow therapeutic index (NTI) and substrate for CYP3A4 MRP-2. Ajuga bracteosa (AB), family Lamiaceae widely used to treat epilepsy, gastric diseases, protects against liver damage in folk. It contains bioactive metabolites, which are powerful inhibitors of CYP3A4, CYP3A5, CYP19, CYP2C19 enzymes P-gp transporter. Concomitant use NTI drugs herbs, like AB increase chances herb-drug interactions (HDIs). This study was aimed analyze crude extract (ABCE) investigate its effect on pharmacokinetics CBZ rats. In pre-treatment study, rats received ABCE (1000 mg/kg) orally 14 days, followed by single dose (80 15th day. co-administration doses were administered concomitantly one session. All 0.5% carboxymethylcellulose (CMC) as vehicle. HPLC analysis showed that contained 1.3 mg/g ursolic acid, 2.1 sitosterol 2.9 stigmasterol. Non-compartmental pharmacokinetic an Cmax, AUC0-∞, MRT, t1/2 decrease tmax, Vd Cl both, pre-treated co-administered groups vs controls. An concentration tissue both well animals observed compared control. The above results suggested possible HDIs between thus, may warrant adjustment epileptic patients simultaneous administration or products.