Prediction of Drug Response and Safety in Clinical Practice

Abstract

Many clinicians hoped that the completion of the Human Genome Project would result in "individualized drug therapy," i.e., determining the right medication at the right dose 100% of the time based upon the individual's genetics. The pharmacogenomic prediction of drug efficacy and safety has not become a reality due to continuing realization of the complexity dictating the human-drug interaction. New methods of metabolomics, proteomics, and transcriptomics that account for this complexity hold promise for translational researchers hoping to increase drug efficacy and decrease drug toxicity.

Serum Metabolomics in Rats after Acute Paraquat Poisoning

“…13,14) In drug-toxicity assessment, metabolomics is often concerned with finding toxicity-related biomarkers by investigating the changes in metabolic signatures induced by drug exposure. 15,16) Principal component analysis of the results of acute paraquat poisoning provided an unsatisfactory separation of data between the acute paraquat poisoning group and the control group.…”

Omics Screening for Pharmaceutical Efficacy and Safety in Clinical Practice

“…More common and less severe toxicities, such as statin-rhabdomyolysis, may be best screened by a combination or syllogistic approach. A biologic systems panel (BSP) [79] has the potential to account for several common genetic polymorphisms, proteomic, and metabolomic variables improving the overall predictive values of the panel. More common toxicities may be cost-effectively screened with an initial genomic screen, followed by a functional screen, if positive on the initial screen, so that patients are not denied therapies due to false positive tests.…”

CYP2C19 drug-drug and drug-gene interactions in ED patients

“…This has important implications for drug effectiveness and safety [1]. Hepatic cytochrome 2C19 (CYP2C19), a CYP450 subtype, metabolizes up to 15% of known pharmaceuticals [2] including drugs with narrow therapeutic windows frequently encountered by physicians such as warfarin, clopidogrel, and carbamazepine (Table 1).…”

“…Knowledge of patient genotypes in the emergency department (ED) may lead to improved efficacy and safety of drugs prescribed in the near future. However, genotyping is not sufficient to predict safety and effectiveness [14], and accounting for clinical factors such as drug-drug interaction may be equally important [1,15]. Therefore, characterizing the frequency of drug-drug interactions and the prevalence of genetic polymorphisms in an ED population allows for an estimation of the implications for drug-gene interaction in ED patients [1,16].…”