Experience gained by wide clinical usage of a drug following marketing may assist in recognising individual risk factors and better definition of safe dosage. Strategies of avoiding the prescription in "at-risk situations" and safer dosage regimes have reduced adverse hepatic reactions due to several drugs. Some such examples include, avoidance of reuse of halothane within 3 months, parenteral administration of large doses of tetracycline as well as its use in pregnancy and renal disease, aspirin in children, and valproic acid in combination therapy in children under 3 years of age
(Farrell, 1994; Neuberger, 1998). The incidence of hepatic fibrosis with weekly low-dose methotrex-ate regimes is much lower than that reported with daily dose regimes (Boffa et al., 1995; Aithal et al., 2001).
Of even greater importance in the determination of individual risk are the inherited factors that affect the kinetics and dynamics of numerous drugs. Susceptibility to hepatic drug reaction depends principally on genetic factors that determine the metabolism, as well as the biochemical and immunological responses, to the metabolites. A major difference between genetic and environmental variation is that an inherited trait has to be tested for only once in a lifetime, whereas environmental effects change continuously. In the future, the discovery of pharmacogenetic traits will change with new technologies based on genomics. Rapid sequencing and single-nucleotide polymorphisms (SNPs) will play a major role in the linking of sequence variations with heritable phenotypes of drug response (Meyer, 2000). In fact, pharmacogenetics technology may enable a significantly better postmarketing surveillance system. In this proposed concept (Roses, 2000) hundreds of thousands of patients who receive the drug would have blood taken and stored in an approved location. As rare, serious adverse events are documented, DNA from patients who experienced the ADR could be compared with that from controls, who did not have adverse reaction while on the drug. This would enable "genetic fingerprints" (SNP profiles) of the subjects susceptible to the adverse event to be determined. These adverse event profiles would be combined with efficacy profiles to produce a comprehensive medicine response profile. This would allow selection of patients for both efficacy and lower complications of drug therapy.
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