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

Biol Pharm Bull. 2015;38(9):1265-71. doi: 10.1248/bpb.b15-00030.

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 (Ka) (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Weight
  • Connective Tissue Diseases / metabolism*
  • Cyclosporine / pharmacokinetics*
  • Female
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Male
  • Middle Aged
  • Models, Biological*
  • Nonlinear Dynamics
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Cyclosporine