The Study On The Effects Of Three Chinese Medicines To The Pharmacokinetics And Pharmacodynamics Of Carbamazepine

AimThe aim of this study was to investigate the effects of the three Chinese medicine on the pharmacokinetics of carbamazepine in mice, examine the the neuroprotective effects of carbamazepine combined with Songlingxuemaikang capsules and Xuemaitong capsules on pentylenetetrazol(PTZ) induced seizures in mice, and study the effects of Songlingxuemaikang capsules on the pharmacokinetics of carbamazepine in the convulsion model mice induced by pentylenetetrazol.Methods1. Kunming mice were divided into five groups. The mice were received carbamazepine orally alone or combined with Ligustrazine Hydrochloride Injection,Songlingxuemaikang capsules, Xuemaitong capsules and verapamil,respectively. Blood and brain tissue samples were collected at different time. After the samples were pretreated, they were detected by HPLC, and the concentration-time curves were obtained. The pharmacokinetic parameters including t1/2β,AUC0-t, Cl, Cmax, Tmax were calculated using DAS2.0.2. Kunming mice were divided into four groups. PTZ was intraperitoneally injected into mice to make the model of convulsion. In the meanwhile, the mice were received normal saline, carbamazepine orally alone or in combination with Songlingxuemaikang capsules and Xuemaitong capsules, respectively. Tonic convulsion latency, level, frequency and duration were observed, attack rate and mortality were calculated, and pathologic study were determined on the12th day.3. PTZ was intraperitoneally injected into Kuming mice to make the model of convulsion. Then the mice were divided into two groups, and received carbamazepine orally alone or combined with Songlingxuemaikang capsules. Blood and brain tissue samples were collected at different time. After the samples were pretreated. they were detected by HPLC, and the concentration-time curves were obtained. The pharmacokinetic parameters including t1/2β,AUC0-t, Cl,Cmax, Tmax were calculated using DAS2.0.Results1.Ligustrazine Hydrochloride Injection could not change the pharmacokinetic parameters of carbamazepine significantly. And Songlingxuemaikang capsules increased the Cmax by25.9%(P<0.05) in mice plasma, and no obvious changes in other parameters were bvserved. However, there had been significant changes in the brain pharmacokinetic parameters, the t1/2β AUC0-t, Cmax of carbamazepine was amplified38.2%,107.6%,99.3%, CL was reduced to108.7(P<0.05). Xuemaikang capsules increased the t1/2β, AUC0-t,Cmaxby31.7%and33.3%,40.2%and170.3%,43.7%and157.8%in plasma and brain, respectively. More over, verapamil could change all the pharmacokinetic parameters but Tmax.2.Tonic convulsion latency and duration were restrain by carbamazepine in mice significantly, and attack rate and mortality was decreased obviously(P<0.05). Carbamazepine combined with Songlingxuemaikang capsules and Xuemaitong capsules could inhibit PTZ-kindling seizures in mice, and better than carbamazepine orally alone. On the pathology, carbamazepine group showed cerebral congested obviously, while brain cells and neuronal degeneration was decreased. These effects were better in carbamazepine combined with Songlingxuemaikang capsules and Xuemaitong capsules group.3.Songlingxuemaikang capsules could change the pharmacokinetic parameters of carbamazepine in PTZ-kinding seizures mice. The capsules increased the Cmax by17.5%and shortened Tmax by35.0%(P<0.05) in plasma, and increased the AUC0-t, Cmax by78.9%and52.9%, decreased CL, Tmax by44.7%and34.6%(P<0.05) in brain, respectively.ConclusionXuemaitong capsules could change the pharmacokinetic parameters of carbamazepine in mice,Songlingxuemaikang capsules could increase the cerebral distribution of carbamazepine in mice.Carbamazepine combined with Songlingxuemaikang capsules and Xuemaitong capsules can significantly suppressed the development of PTZ induced seizures in mice. In addition, Songlingxuemaikang capsules could change the pharmacokinetic parameters of carbamazepine in PTZ-kinding seizures mice. The study provided an experimental basis for Chinese medicine to cure epilepsy, meanwhile contribute a new theoretical foundation for the study of Chinese medicine with P-gp inhibitory activity.