Pharmacokinetics And Pharmacodynamics Studies Of Lopinavir In Chinese Adults With HIV-1 Infection

ObjectivePharmacokinetic profiles of lopinavir in Chinese HIV-infected patients were evaluated and observed in present study.To explore the viralogical efficancy with compliance in long-term treatment by detecting the plasma concentrations of lopinavir(LPV) in HIV-infected patients.MethodsA total of 16 patients were enrolled into the LPV pharmacokinetic study. Blood samples were collected before and 0.5,1,1.5,2,2.5,3,4,6,8,10 and 12h after administration and determined by using the developed HPLC method. The pharmacokinetic profiles were assessed by WinNonlin software.84 ART-experienced patients administrated with TDF+3TC+LPV/r were followed up for 96 weeks. HIV-1 VL and plasma lopinavir concentration were measured at each subsequent visit.ResultsThe non-compartment model PK parameters were as follows:Tmax (3.88±0.23h),Cmax (10.36±3.42μg/mL),Cmin (2.18±0.34μg/mL),AUC0-24 (116.22±15.68μg*h/mL),T1/2 (4.5±0.13h),CL/F (3.44±1.34 L/h) respectively. Tmax of LPV in TDF group and AZT group are 4.01±0.43h and 3.38±0.52h respectively (p=0.048);AUClast are 64.44±27.25 and 75.32±19.48(μg*h/mL) (P=0.024), as well as AUCINF are 109.92±26.43 and 137.68±37.79(μg*h/mL) respectively (p=0.028)Virological failure(VF) occurred in 11patients, while 73 patients had virological respond(VS). In VS group, the median VL decreased to <40 copies/ml after 24 weeks treatment, and the plasma lopinavir concentration at each visit were higher than 1.0 μg/ml. The absence of drug levels in 72.7%(8/11) patients indicated poor adherence. A total of 17 patients presented drug levels<1.0 μg/ml for more than once during the visits, the rates of Cmin<1-0 μg/ml were positive correlated with VF (r2=0.9418).When the rates ≤10%, only 4.5% of patients meet VF.ConclusionThe profiles of the pharmacokinetics of lopinavir in Chinese HIV-1 infected patients demonstrate lower Cmin than those reported in foreign studies, while other parameters are similar. Co-administrated with TDF, Tmax of LPV is longer than that in AZT group, while lower bioavailability has been shown in TDF group than in AZT group. Successful management of adherence should be valued due to the slightly higher Cmin man minimum effect concentration.It is a simple way of evaluating the adherence by monitering the plasma concentration. The plasma lopinavir levels were higher than 1.0 μg/ml with good adherence. Virological failure may be in pace with poor adherence. Low drug levels may be positive correlated with virological failure.