Population Pharmacokinetics Of Atorvastatin In Hyperlipoidemia

ObjectiveTo evaluate the population pharmacokinetics (PPK) of atorvastatin in Chineseinpatients with hyperlipoidemiaMethods1. To establish HPLC-UV method for determination of atorvastatin in human plasma.Chromatography was carried out on a Nova-pak C18column (3.9×150mm,4μm),using methanol-0.02mol·L-1ammonium acetate buffer (70:30, V/V) as mobilephase at a flow rate of0.9mL·min-1.The detection wavelength was set at245nm.Column temperature was kept at30℃. Plasma samples were extracted by ethylacetate and analyzed after been concentrated. Progesterone was used as the internalstandard.2. One hundred and ten blood samples of atovastatin in steady state were collectedfrom one hundred and seven hyperlipoidemia inpatients. The plasma concentrationsof atorvastatin were determined by HPLC-UV method. The influence of the fixedeffects on clearance of ATV was investigated using NONlinear mixed effects model(NONMEM).Results1. The regressive equation for atorvastatin was=0.1366x+0.0484(r=0.9992) over therange of1.0～535.0ng·mL-1. The detection limit was0.5ng·mL-1(S/N≥3). Theaverage recovery rates of atorvastatin at2.0,201.1,535.0ng· mL-1were100.8%,101.1%and99.5%respectively. Intra-and inter-day RSD was less than2.80%.2. The final regression model of ATV was: CL(L h-1)=θCL×(WT/62)ΘWT, V (L) V,.It was found that weight of patient has a significant influence on the clearance ofATV. Validation studies confirmed the internal stability, validity and predictiveperformance of the model. Conclusion1. With the accurate, rapid and stable characters, the established HPLC-UV method issuitable for the determination of concentrations of atorvastin in human plasma.2. By using the established PPK model of atorvastatin, patience’s clearance can beachieved according to the weight, which will be helpful for the individualizeddosing regimens for atorvastatin in hyperlipoidemia.