Studies On The Pharmacokinetics And Pharmacodynamics Of Drugs Used For HAART In Chinese Patients

Background and ObjectiveHighly active antiretroviral therapy is considered the effective way of HIV / AIDS current treatments, and it has fundamentally changed the process of human HIV infection. Individual differences between the pharmacokinetics of drugs and many other factors play a role in the body in the course multi-drug combination. In order to improve treatment outcomes, reduce toxicity, increase efficacy, TDM help to adjust the individual dose. Since 2003, China began to promote free efficient anti-viral treatment, and in domestic large prospective study China-made generic drugs has been proved effective. It is lacked of the effective plasma concentration data of all types drugs used currently objected on Chinese patients. Our object is the steady-state pharmacokinetics characteristics and pharmacodynamic characteristics of these drugs.Materials and MethodsIn pharmacokinetics studies, we choose 23 inpatients of PUMCH clinic randomly. All of them have been HAART over 6 months, and sign notification. We collect 4ml blood at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14.5, 24, 26.5 hours after taking drugs. And we analyse pharmacokinetics characteristics of AZT, 3TC, NVP, and EFV respectively.In pharmacogynamics studies, we choose 75 outpatients of PUMCH clinic randomly. All of them have been HAART over 6 months, and sign notification. We collect 4ml blood before and 2 hours after taking drugs. Then we analyse pharmacogynamics characteristics of AZT, 3TC, NVP, and EFV respectively. ResultsWe first established methods applied to clinical HAART drug concentration monitoring, widely used to detect seven kinds drugs of three types, simple, sensitive, reproducible, high-efficiency, and easy to start in China.Zidovudine generic-drug appears good absorption and distribution, as good as trade-drug, and meets the needs of HARRT. And the tough plasma concentration of AZT has significant correlation with cholesterol and triglyceride. Both Tmax and AUCo-24 of lamivudine show significant differences between the Chinese and Caucasians. And two ways of Lamivudine dosages have equal effective pharmacokinetics parameters. The nevirapine concentration of Chinese is remarkably high than reported by European. Further research must be done to affirm the effective concentration in Chinese, avoiding side effects. Tough concentration of nevirapine has correlation with liver functional parameters. Efavirenz shows high Cmax than European, while meets the effective concentration properly.ConclusionsOur study established three HPLC methods to detect the drug concentration in plasma, calculate pharmacokinetics parameters of four kinds of anti-virus treatment for drugs, as well as pharmacodynamics characteristics of three of them. Our complete data supply substantial foundation for HAART drug monitoring.