Main Research Interests
- Role of transporters in drug efficacy and toxicity
- Drug absorption and delivery
- Renal and hepatic elimination
- Uric acid transporters
- Drug-drug interaction on transporters
- Species difference of drug transporters
- Regulation of transporter activity
- Interaction between transporters and PDZ proteins
- Transporter-related nonlinear pharmacokinetics
- Drug-induced organ toxicity
Outlines of Researches
The key words of our research are, "Transporter", "Pharmacokinetics", and "Xenobiotics". More than 400 transporters are expressed in human and playing roles in regulating membrane permeation of various types of substances, including physiological compounds and xenobiotics such as clinically used drugs. Some transporters affect pharmacokinetic properties of drugs, and others are physiologically essential, since genetic mutation of those transporters directly related hereditary diseases. So, transporters are very potential as the novel targets for drug development, drug delivery and optimization of clinical dosage regimen.
Based on such background, following research themes are under investigation:
- Drug-induced toxicities.
- Uric acid transporters and drug-induced alteration of serum uric acid level.
- Drug-induced lung toxicity.
- Novel drug targets.
- Anticancer drugs targeting cancer-selective transporters.
- Markers of novel kidney function
- Inflammation related transporters
- Transporters regulating carnitine and related compounds
- Species differences in drug transporters.
- Hepatic OATP transporters
- Intestinal OATP and efflux transporters and bioavailability.
- Transporter-protein interaction.
- Roles of PDZ proteins in transport activity
- Identification of proteins interacting with transporters
Typical transporters under investigation are as follows:
- Physiological Transporters: CTL, OCTNs, MCTs, NPT, PEPTs, PGT, SGLT, SMCT, URAT1.
- Drug Transporters: OATPs, OATs, OCTs, BCRP, MDRs, MRPs.
- Matsunaga N., Nunoya K., Okada M., Ogawa M., Tamai I. Evaluation of hepatic disposition of paroxetine using sandwich-cultured rat and human hepatocytes. Drug Metab. Dispos., 41: 735-743, 2013.
- Nakanishi T., Hasegawa Y., Haruta T., Wakayama T., Tamai I. In vivo evidence of organic cation transporter-mediated tracheal accumulation of the anticholinergic agent ipratropium in mice. J. Pharm. Sci., 102: 3373-3381, 2013.
- Shirasaka Y., Shichiri M., Kasai T., Ohno Y., Nakanishi T., Hayashi K., Nishiura A., Tamai I. A role of PGT in regulating PGE2 release from BEAS-2B cells in response to LPS. J. Endocrinol., 217: 265-274, 2013
- Nakanishi T., Ohya K., Shimada S., Anzai N., Tamai I. Functional cooperation of URAT1 (SLC22A12) and URATv1 (SLC2A9) in renal reabsorption of urate. Nephrol. Dial. Transplant., 28: 603-611, 2013.
- Tamai I., Nakanishi T. OATP transporter-mediated drug absorption and interaction. Curr. Opin. Pharmacol., 13:859-863, 2013
Ikumi TAMAI Professor
Membrane Transporters, Drug Absorption and Disposition
Yoshiyuki SHIRASAKA Associate Professor
Drug Absorption, Pharmacokinetics, Biopharmaceutics
Hisakazu KOMORI Assistant Professor
Pharmacokinetics, Biopharmaceutics, Molecular Biology