Population Pharmacokinetic Analysis of Oral Tacrolimus in Patients with Glomerulonephritis

Abstract

Objective: Tacrolimus as an immunosuppressant is used to treat for several types of glomerulonephritis. Narrow therapeutic window and huge interindividual variability of tacrolimus make it impossible to predict its serum level. Hence, the purpose of this study was to derive population pharmacokinetic model for tacrolimus in glomerulonephritis patients. Materials and methods: Adult patients diagnosed with glomerulonephritis and treated with oral tacrolimus were included. Electronic medical records were reviewed retrospectively to access clinical findings and demographic data. Population pharmacokinetics of tacrolimus was evaluated using nonlinear mixed effect model by first-order conditional estimation with interaction algorithm. Results: One hundred and forty-five patients were included in this study and one thousand and nine hundreds thirty-eight blood samples were analyzed. The estimated apparent clearance (CL/F) was 19.5 L/h, and apparent volume of distribution (V/F) was 380 L. The final model suggested that serum creatinine levels were negatively correlated with both CL/F and V/F whereas serum albumin levels were positively associated with V/F. Conclusion: Various factors affecting tacrolimus pharmacokinetics were explored. The findings of this study pointed out that tacrolimus pharmacokinetics were related to patients' kidney function and serum albumin level in glomerulonephritis patients. Developed model may guide individualized tacrolimus therapy in glomerulonephritis patients and improve therapeutic outcomes in glomerulonephritis patients.