TY - JOUR
T1 - Population pharmacokinetic approach to the use of low dose cyclosporine in patients with connective tissue diseases
AU - Tsuji, Yasuhiro
AU - Iwanaga, Nozomi
AU - Mizoguchi, Akiko
AU - Sonemoto, Emi
AU - Hiraki, Yoichi
AU - Ota, Yukio
AU - Kasai, Hidefumi
AU - Yukawa, Eiji
AU - Ueki, Yukitaka
AU - To, Hideto
N1 - Publisher Copyright:
© 2015 The Pharmaceutical Society of Japan.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
KW - Connective tissue disease
KW - Cyclosporine
KW - Dosing strategy
KW - Nonlinear mixed effects modeling
KW - Population pharmacokinetics
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U2 - 10.1248/bpb.b15-00030
DO - 10.1248/bpb.b15-00030
M3 - Article
C2 - 26328482
AN - SCOPUS:84941144540
SN - 0918-6158
VL - 38
SP - 1265
EP - 1271
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 9
ER -