Population pharmacokinetic approach to the use of low dose cyclosporine in patients with connective tissue diseases

Yasuhiro Tsuji, Nozomi Iwanaga, Akiko Mizoguchi, Emi Sonemoto, Yoichi Hiraki, Yukio Ota, Hidefumi Kasai, Eiji Yukawa, Yukitaka Ueki, Hideto To

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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.

Original languageEnglish
Pages (from-to)1265-1271
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume38
Issue number9
DOIs
Publication statusPublished - 2015 Sep 1
Externally publishedYes

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Keywords

  • Connective tissue disease
  • Cyclosporine
  • Dosing strategy
  • Nonlinear mixed effects modeling
  • Population pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Tsuji, Y., Iwanaga, N., Mizoguchi, A., Sonemoto, E., Hiraki, Y., Ota, Y., Kasai, H., Yukawa, E., Ueki, Y., & To, H. (2015). Population pharmacokinetic approach to the use of low dose cyclosporine in patients with connective tissue diseases. Biological and Pharmaceutical Bulletin, 38(9), 1265-1271. https://doi.org/10.1248/bpb.b15-00030