Page - (000103) - in Biomedical Chemistry: Current Trends and Developments

Even after receiving approval to be marketed, a drug must continue to be evaluated by an appropriate pharmacovigilance system. Indeed, as a much larger number of patients begin to use the drug, companies must continue to monitor it carefully in order to evaluate long-term safety and the effect of the new drug in specific subgroups of patients. Importantly, although several new drugs are brought to the market and help fight many diseases, ADME processes of a drug may differ among individuals, resulting in differences in the relationship of drug plasma concentrations and dosage administered. Since inter-individual differences may occur due to differences in age, weight, genetic polymorphism, co-morbid diseases and DDI, drug posology regimen is frequently individualized and TDM plays a very important role in this personalized medicine field. Its major objective is to ensure that drug concentrations are within a defined optimal therapeutic range to maximize drug efficacy, minimize drug toxicity and reduce therapeutic costs. In practice, it involves the measurement of drug concentrations in plasma or serum samples, and the interpretation of these results in an attempt to adjust the dose to that particular patient. Not all drugs are candidates for TDM, as it must meet the following criteria: (1) a narrow therapeutic range; (2) significant inter-individual variability in systemic exposure at a given dose; (3) a clear relationship between blood exposure and clinical effect; and (4) a validated bioanalytical method to measure drug concentration in plasma or serum. 2.1.3 Bioanalysis and Validation Requirements on DDD As described in the previous section, in an attempt to diminish the attrition rate of DDD process, the pharmaceutical industry has put more emphasis on pharmacokinetic evaluation in the beginning of NCEs discovery. Consequently, bioanalysis emerged as an essential support tool to characterize ADME/pharmacokinetics of NCEs through all stages of DDD and not only in the development ones. Around the world, bioanalysis shares the main goal of quantifying drugs (and/or metabolites) in biological matrices, ensuring that high-quality data for valid scientific decision making is obtained. For that, several initiatives