Population Pharmacokinetic Approach to the Use of Low Dose Cyclosporine in Patients with Connective Tissue Diseases

Abstract

This study describes the population pharmacokinetics and dose personalization of cyclosporine in 36 patients with connective tissue diseases. A one-compartment open model with absorption was adopted as a pharmacokinetic model, and a nonlinear mixed effects model was used to analyze the population pharmacokinetic models. In the final model, age (AGE) and total body weight (TBW) were influential covariates on clearance (CL/F), which was expressed as CL/F (L/h)=17.8×(AGE/60)^−0.269×(TBW/46.9)^0.408, in addition to the volume of distribution (Vd/F), (L)=98.0 and absorption rate constant (K_a) (h⁻¹)=0.67 (fixed). The results of the present study provide novel insights into factors involved in determining the most suitable dose and dosing strategy for individual patients with connective tissue disease.