Clinical Pharmacology and Therapeutics

kao Kazuo Matsubara, Ph.D. Professor  btn

The aim of our laboratory is to establish the scientific bases of appropriate drug usage and pharmaceutical practice. The efficacy and safety of drugs are closely related to their pharmacokinetics and pharmacodynamics. We have systematically developed the research from drug transport analyses based on the molecular levels to the clinical pharmacokinetics. (Figure 1). We are also trying to elucidate the mechanisms underlying adverse effects of anti-cancer reagents (Figure 2). To settle the problem found in the pharmacotherapy, we attempt to feedback the achievements of basic research to clinical practice.

Research and Education

Our research projects have been carried out to determine optimal drug therapies in view of pharmacokinetics, having with the theme “laboratory and clinical studies of the pharmacokinetics, effectiveness and toxicity of drugs”. We have performed functional and molecular characterization of drug transporters expressed in the intestine, kidney and liver, and the establishment of personalized medicine based on the molecular information of drug transporters.
Furthermore, we contribute to personalized medicine of immunosuppressant tacrolimus in the living donor liver transplantation (LDLT). It was demonstrated that the intestinal expression level of MDR1 is a part of prognostic factor for acute cellular rejection and mortality as well as a pharmacokinetic factor in recipients of LDLT (Figure 2).
We also investigate personalized medicine of anticancer drugs to improve safety and efficiency of chemotherapy, and recently investigate proper usage of dopamine agonists in Parkinson’s disease. The graduate students of Medicine and Pharmaceutical Sciences play pivotal roles for laboratory research, and all members have been tackling with difficult scientific problems, collaborating with pharmacists in Kyoto University Hospital.

薬剤Figure 1. Research on drug transporters –from bench to bedside–

薬剤2Figure 2. Reverse translational research for adverse effects of anti-cancer drugs


Recent Publications

  1. Otani Y, Yonezawa A, Tsuda M, Imai S, Ikemi Y, Nakagawa S, Omura T, Nakagawa T, Yano I, Matsubara K: Time-Dependent Structural Alteration of Rituximab Analyzed by LC/TOF-MS after a Systemic Administration to Rats. PLoS One: 12(1):e0169588 (2017).
  2. So K, Tei Y, Zhao M, Miyake T, Hiyama H, Shirakawa H, Imai S, Mori Y, Nakagawa T, Matsubara K, Kaneko S: Hypoxia-induced sensitization of TRPA1 in painful dysesthesia evoked by transient hindlimb ischemia/reperfusion in mice. Sci Rep 6: 23261 (2016)
  3. Imai S, Ikegami D, Yamashita A, Shimizu T, Narita M, Niikura K, Furuya M, Kobayashi Y, Miyashita K, Okutsu D, Kato A, Nakamura A, Araki A, Omi K, Nakamura M, James Okano H, Okano H, Ando T, Takeshima H, Ushijima T, Kuzumaki N, Suzuki T, Narita M: Epigenetic transcriptional activation of monocyte chemotactic protein 3 contributes to long-lasting neuropathic pain. Brain, 136: 828-843 (2013)
  4. Nishihara K, Masuda S, Shinke H, Ozawa A, Ichimura T, Yonezawa A, Nakagawa S, Inui K, Bonventre JV, Matsubara K: Urinary chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) as a tubular injury marker for early detection of cisplatin-induced nephrotoxicity. Biochem Pharmacol, 85: 570-582 (2013)
  5. Omura T, Asari M, Yamamoto J, Kamiyama N, Oka K, Hoshina C, Maseda C, Awaya T, Tasaki Y, Shiono H, Shimizu K, Matsubara K. HRD1 levels increased by zonisamide prevented cell death and caspase-3 activation caused by endoplasmic reticulum stress in SH-SY5Y cells. J Mol Neurosci, 46: 527-535 (2012)

Clinical Pharmacology and Therapeutics

Professor:Kazuo Matsubara, Ph.D.
Associate Professor:Takayuki Nakagawa, Ph.D., Satoshi Imai, Ph.D.
Assistant Professor:Tomohiro Omura, Ph.D., Shunsaku Nakagawa, Ph.D., Yuki Otani, Ph.D.
TEL:+81-75-751-3577
FAX:+81-75-751-4207
e-mail:kmatsuba@kuhp.kyoto-u.ac.jp
URL:http://www.kuhp.kyoto-u.ac.jp/~yakuzai/english/index.html