ABSTRACT
Objective:To explore the effect of P-glycoprotein ( P-gp) activity on its mediated imatinib mesylate accumulation and intracellular drug membrane permeability. Methods: 1199G/wt ABCB1 and 1199A/mut recombinant plasmids were transferred into HEK293 cells, respectively, and the expression levels of mRNA in different cell models were investigated by RT-PCR. Cell Counting Kit-8(CCK-8) assay was used to detect the drug toxicity in different cell models, HPLC was applied to determine the drug concentra-tion in different cell models and evaluate the intracellular accumulation, and transmembrane resistance experiment was employed to de-tect the transmembrane permeability and evaluate the effect of P-gp activity on drug transportation. Results: Cytotoxicity test showed that the drug concentration in the transferred cells was lower than that in the control group, which proved that P-gp had the function of mediating drug out of cells. HPLC and transepithelial electrical resistance experiment showed that compared with the wild type of AB-CB1 (1199G) cells, mutation of ABCB1 1199A cells had stronger effect on P-gp mediated mesylate imatinib accumulation and drug membrane permeability. Conclusion:The experiment manifested that ABCB1 (1199G/A) site mutation can change the coding protein P-gp activity and the polymorphisms will lead to the increase of mesylate imatinib clearance rate and the decrease of effective drug con-centration in target cells. Meanwhile, the clarification of ABCB1 genetic types in clinics can guide the individualized medication of imatinib mesylate.
ABSTRACT
Valproic acid is a first-line broad-spectrum antiepileptic drug, however, the pharmacokinetics of valproic acid are affected by many factors, such as heredity, drug combination and so on. So, how to realize the individualized dosing regimen of valproic acid has received much attention. Population pharmacokinetics combines classical pharmacokinetic principles and population statistical models to quantitatively evaluate the influence factor of drug concentration in the patient population. Thus, it can optimize characterization of the differences among individuals. This article reviews the researches about valproic acid in recent years, and summarizes the effect of the factors on the metabolism of valproic acid, such as drug combination and gene polymorphism. Additionally, focus on the latest research progress of individual administration of valproic acid under the guidance of population pharmacokinetics.
ABSTRACT
Valproic acid is a first-line broad-spectrum antiepileptic drug, however, the pharmacokinetics of valproic acid are affected by many factors, such as heredity, drug combination and so on. So, how to realize the individualized dosing regimen of valproic acid has received much attention. Population pharmacokinetics combines classical pharmacokinetic principles and population statistical models to quantitatively evaluate the influence factor of drug concentration in the patient population. Thus, it can optimize characterization of the differences among individuals. This article reviews the researches about valproic acid in recent years, and summarizes the effect of the factors on the metabolism of valproic acid, such as drug combination and gene polymorphism. Additionally, focus on the latest research progress of individual administration of valproic acid under the guidance of population pharmacokinetics.
ABSTRACT
AIM:Base on individual antihypertensive drugs therapy related genotyping microarray, with platform of Microsoft Visual Basic 6.0,developed hypertension microarray data analysis system vl.0.By reading GPR or LSR file produced by microarray scanners,the system automatic determine microarray validity,generate relative genetype result and store for later database manage.METHODS:The Microsoft Visual Basic V6.0 was used for programming tools.RESULTS.After analysised 1025 microarray, the results showed that system run smoothly and reliable,greatly increased the analysis efficiency. CONCLUSION:Software design succeed, achieved the desired objectives.