Altered drug metabolism during pregnancy
Medication use in pregnancy is prevalent due to pre-existing medical conditions or newly developing disorders. This unavoidable drug treatment requires accurate pharmacokinetic information because under- or over-exposure may result in detrimental clinical outcomes not only to the mother, but also to the fetus. In fact, pharmacokinetic profiles of many drugs are altered during pregnancy. Generally, oral absorption of drugs is delayed, and distribution and renal excretion of drugs increase. Changes in hepatic drug metabolism, on the other hand, are not well understood. Clinical data suggest metabolic pathway-dependent changes in hepatic clearances of drugs in pregnancy. However, it is currently unclear whether the clinical data reflect true changes in expression and function of hepatic drug metabolizing enzymes, apart from changes in other factors influencing hepatic clearances, such as plasma protein binding or hepatic blood flow. Also unknown is the potential mechanism of altered drug metabolism in pregnancy, if there is any. To date we have studied to identify factors responsible for altered drug metabolism during pregnancy and elucidate the underlying mechanisms.
Characterization of preclinical pharmacokinetics for drug candidates
Preclinical characterization of pharmacokinetics of a drug candidate is essential in drug development processes for optimization of “druggability” of compounds. We have provided our expertise in preclinical pharmacokinetics for development of antiviral and antibiotic agents.
Clinical pharmacology: pharmacogenetics and pharmacokinetics
Pharmacokinetic profiles of drugs are influenced by various factors such as genetic make-up of a person. For example, presence of certain genetic variants in drug metabolizing enzymes (e.g., CYP2C9*8) is associated with lower maintenance doses of warfarin in African Americans. We have been investigating the molecular mechanisms underlying the effects of genetic variations on pharmacokinetics of drugs.