| AIM 1. To investigate the dynamic correlation of the CBZ concentrations between in saliva and in blood during absorption, distribution, metablism and excretion of the drug in the human body by comparing the pharmacokinetics of two CBZ preparations (Tegrotol and Carbamazepine tablet). 2. To estimate the influence of the main factors such as sampling methods, diurnal rhythm, flow rate and components of saliva, sex and age of patients on it and provide the scientific basis for using saliva to monitor clinic therapeutic drug concentration. METHODS:1. Set up the analytic methodology: A quantitative analytic method for CBZ in body fluid was set up by HPLC. The system application was inspected by column efficacy and separate efficacy test; the linear scope, more over, the detection limit, standard curve, and the experiments for precision and recovery rate were used to evaluate this method comprehensively.2. Study of pharmacokinetics correlation between degretol and cabamazepine tablet: Using the cross-over with auto-control experiment, 8 healthy volunteers were divided into two groups, which took the tegrotol and carbamazepine tablets (200 mg each) in turn respectively, saliva (under nature condition) and blood samples were collected simultaneouslly after medication 1.5, 3, 4.5, 6, 7.5, 9, 10.5, 12, 24, 72, 144, 216, 312 h. The CBZ concentrations in all samples were detected by HPLC in order to observe the dynamic correlation during the course of CBZ in the body, calculate the pharmacokinetic parameters respectively, and compared them between different samples and different preparations.3. Study of the influential factors on saliva CBZ concentration: CD The saliva samples were collected by three methods (Nature, Cotton ball and Citric acid) in turn from 12 epileptic patients with blood samples collected simultaneously in order to study the influence of sampling methods on CBZ concentration in saliva. ?The Cotton Ball was used to collect 8 patients' saliva in 4 time points within 24 hours (7:00,11:00,15:00,21:00), and blood samples collected simultaneously in order to study the influence of daily biorhythm on saliva CBZ concentration. (? Paired parotid saliva and blood samples were collected from 12 patients under the conditions stimulated by 0.5% and 2% citric acid and after the stimulation in order to study the influence of the parotid saliva's flow rate on the saliva CBZ concentration. ?Using the cross-over experiment, 12 healthy volunteers were divided into two groups, whose paired saliva and venous blood samples were collected in turn respectively in order to study the influence of the saliva components on the saliva CBZ concentration. (5) 70 patients were divided into 3 groups according to the aging stage of 3-7, 8-28,29-63, equal proportion of male and female were in each groups. Paired saliva and blood samples were collected in order to study the influence of age between groups and the discrepancy of sex within each groups on saliva CBZ concentration. RESULTS:1. In this experiment, the number of theoretical plate was 2986,6, the CBZ in saliva and blood were separated on the baseline, and its specificity was wonderful; in the scope of 0.228-3.99 ug.mL"1 in saliva and of 2.68-17.54 ug.mL"1 in blood, there were a good correlation between CBZ concentration and the score of peak area, the detection limit was 0.03 ug.mL"1 (S/N>3); regression equation of saliva was C=4.8I2 X 10'6A-0.0215 (r=0.9999, n=5) , the one of blood was C=6.826X 10~6A-0.0141 0=0.9994, n=5), Intra-assay and Inter-assay precisions were less than 5.5%; the methodology recovery rates were all above 97%.2. Within 3-144 h of tegretol and 3-24 h of carbamazepine medication, there was a high correlation of CBZ concentration between in saliva and blood (r value were 0.905 and 0.872). The concentration-time curves of both preparations could be imitated by open one-compartment model, the Tmaxx k&^ T\n\x^ CL/F calculated from saliva and blood of each preparations had no statistic difference; Tmax and T^ka of tegretol ar...
|
PDF Full Text Request