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Clinicial Pharmacology and Toxicology

Research activities

Research Areas of Focus:

The research programs focus on drug metabolizing enzymes and its regulation, drug transporters, placental and mammary gland drug transport and metabolism, and reproductive toxicology teratology.

Shinya Ito

Head - Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children (SickKids), University of Toronto.

Dr. Ito's research has focused on Clinical Pharmacology, Drug Transport and Kinetics, and Human Milk.

1. Research Endeavours

a) Breastfeeding pharmacology. This research focus is closely tied with clinical activities in the Motherisk program in collaboration with Dr. Koren. Studies include prospective cohort studies on drug safety during lactation. With many new medications introduced in the market, or about to be introduced in the market, clinical data on safety and information on drug concentration in milk provide previous evidence for rationale therapeutics. In addition, the scope of this program has recently been expanded to economic impact of maternal drug therapy during breastfeeding. Dr. Ito's research group is especially interested in antidepressant therapy.

b) Transport of xenobiotics. Funded mainly by CIHR, this basic research program has investigated various aspects of drug transporters such as P-glycoprotein and organic cation transporters. Current work focuses on drug transfer mechanisms of the mammary gland and its organic cation transporters such as OCTN1, and OCTN2. The ultimate goal is to reveal localization of these transporters in the polarized membrane structures of lactating mammary gland.

c) Effects of milk on development of detoxification mechanisms. The Ontogeny of drug metabolizing enzymes and transporters in the intestine and the liver of the infant remains obscure. This research program funded by CIHR has just begun to explore influences of human milk and its alternatives (i.e., formula) on development of cytochrome P450 enzymes and major drug transporters such as MDR1 P-glycoprotein, MRP2, and PEPT1. In order to elucidate their respective regulatory mechanisms, and to identify responsible compounds in milk, we are using reporter assay for aryl-hydrocarbon receptor (AhR) and SXR/PXR activation. This research is being carried out in collaboration with Drs. P. Harper, H. Yeger, D. O'Connor at SickKids, and Dr. Loddernel at UC Davies.