Population Pharmacokinetics of Tacrolimus in Whole Blood and Plasma in Asian Liver Transplant Patients

摘要: The objectives of this study were to develop population pharmacokinetic models tacrolimus in an Asian with whole blood and plasma drug concentration data, compare the variability parameters these two matrices search for main patient characteristics that explain parameters. Prospective assessment followed by model fitting. Whole samples from 31 liver transplant patients a local hospital receiving oral as part their immunosuppressive therapy assessed. Plasma 29 also evaluated. Concentrations determined electrospray high-performance liquid chromatography tandem mass spectrometry. Two hundred thirteen 157 concentrations used building nonlinear mixed-effects describe disposition plasma, respectively. Covariates investigated included demographic characteristics, biological markers renal functions, corticosteroid dose haematological parameter. A one-compartment was concentration-time data after administration. For model, estimates first-order absorption rate constant (ka), apparent clearance based on administration (CLB/F) volume distribution (Vd,B/F) 2.08h−1, 14.1L/h 217L, coefficient variations (CVs) interpatient variabilities CLB/F Vd,B/F 65.7% 63.8%, Bodyweight, function influenced CLB/F, while height haematocrit Vd,B/F. residual (unexplained) 34.8%. ka, (CLp/F) (Vd,p/F) 5.21h−11, 537 L/h 563L, CVs CLp/F Vd,p/F 96.0% 105.4%, Bodyweight found influence CLp/F, erythrocyte-to-plasma ratio Vd,p/F. 49.8% at mean 1.1 ng/mL. adult paediatric developed using prospective clinical setting. This has identified quantified sources interindividual Vd,B/F, patients. Information derived may subsequently be clinicians dosage individualisation through Bayesian forecasting.