Pharmacogenomics Dictate Pharmacokinetics: Polymorphisms in Drug-Metabolizing Enzymes and Drug-Transporters

摘要: The discovery of a drug is focused on the goal producing useful therapeutic agent through process utilizing multiple skills and expertise basic scientists, pharmaceutical chemists, toxicologists, clinical investigators, governmental regulators clinicians (Mager DE, 2009; Michel MC, Nagase H, 2011). Drug development its evaluation thus very lengthy expensive endeavor. One has to first come up with novel mechanism, identifying relevant target(s) pathway(s) towards formulation new chemical entity (NCE) treat disease. Both in vitro vivo models that are disease form basis preclinical testing identification lead compounds, an Investigational New (IND), ultimately entry only select few into human trials. Therefore, initial studies developments involve synthesis extraction their biological screening pharmacological testing, followed by small animal model toxicology safety profiles. These early pharmacokinetic (PK) measurements guide researchers formulate effective dosage, stability, elimination eventually index compound(s). In pre-clinical studies, favorable PK outcome can FDA approval for phase-I, -II -III (Fasolo A, 2009). However, even after approval, drugs have be continuously monitored improvements bioavailability, therapeutic, toxicologic differences especially large patient population patient-specific variability. For example, azathioprine mercaptopurine intolerance patients were found linked deficiency metabolic enzyme, thiopurine S-methyltransferase, formed genetic molecular diagnostic test designate specific (Yates CR, et al. 1997). Thus, before humans start, significant body data must compiled appropriate dose should established ensure safety. Toxicology, pharmacology sciences all represent core pre-