Research on the effects of chemical substances on children, elderly
people,and those with gene disorders
Title of Research:
13_PT03-01
Quantitative prediction of the pharmacokinetics of chemical substances by the use ofmathematical model with considering the age-dependent functional changes of metabolic
enzymes and transporters
Principal Investigator:
Hiroyuki Kusuhara, PhD (Professor, Laboratory of Molecular Pharmacokinetics, Graduate
School of Pharmaceutical Sciences, The University of Tokyo)
7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033, Japan(tel) +81-3-5841-4770 (e-mail) kusuhara@mol.f.u-tokyo.ac.jp
Collaborators:
Kazuya Maeda, PhD (Associate Professor, Laboratory of Molecular Pharmacokinetics, Graduate
School of Pharmaceutical Sciences, The University of Tokyo)
7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033, Japan(tel) +81-3-5841-4772 (e-mail) kmaeda@mol.f.u-tokyo.ac.jp
Yuichi Sugiyama, PhD (Laboratory Head, Sugiyama Laboratory, RIKEN Innovation Center,RIKEN Research Cluster for Innovation, RIKEN)
1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan(tel) +81-45-503-9211 (e-mail) ychi.sugiyama@riken.jp
Ichiro Ieiri, PhD (Professor, Department of Clinical Pharmacokinetics, Graduate School of
Pharmaceutical Sciences, Kyushu University)
3-1-1 Maidashi, Higashi-ku Fukuoka 812-8582, Japan(tel) +81-92-642-6656 (e-mail) ieiri-ttr@umin.ac.jp
Summary of Research:
To predict the effect of age on the pharmacokinetics of chemical substances, a clinical study will
be performed to evaluate the molecular functions of metabolic enzymes and transporters ofchemical substances with probe drugs. By mathematical modeling, pharmacokinetic data in elder
people can be predicted based on PKs in healthy volunteers. In this year, Cluster Newton Method
was created for rational settings of model parameters and its effectiveness was proven. Moreover,
we performed in vitro experiments to characterize the property of probe drugs for various
molecules such as CYP2E1 and OCT1 and also prepared for the future clinical study.
Timeline: November 1, 2013Topics: NonePublications:Kazuya Maeda, “Quantitative prediction of the impact of drug transporter function on human invivo pharmacokinetics”, 7th Young Investigators Symposium on Clinical Pharmaceutical Sciences,Sendai, 2013.11
Kazuya Maeda, Kenta Yoshida, Akihiko Konagaya, Hiroyuki Kusuhara, “Integrative analyses of thedrug –drug interactions with Cluster Newton Method”, 29th APSTJ Annual Meeting, Saitama,
2014.5
Xuan Zhang, Kazuya Maeda, Hiroshi Suzuki and Hiroyuki Kusuhara, “Contribution of hepatic
OCT1 to the pharmacokinetics of triptans”, 29th APSTJ Annual Meeting, Saitama, 2014.5
Kazuya Maeda, Kenta Yoshida, Yuichi Sugiyama, Akihiko Konagaya and Hiroyuki Kusuhara,“Precise estimations of the inhibition constants by PBPK analyses of metabolites’ pharmacokinetic
alterations using Cluster Newton Method”, 19th North American ISSX Meeting/29th JSSX Meeting,
San Francisco, CA, USA, 2014.10
Xuan Zhang, Kazuya Maeda, Hiroshi Suzuki and Hiroyuki Kusuhara, “Hepatic Organic Cation
Transporter 1 (OCT1) Regulates the Hepatic Clearance of Triptans, But Not Beta-blockers”, 19thNorth American ISSX Meeting/29th JSSX Meeting, San Francisco, CA, USA, 2014.10