Abstract :
The clinical application of new antineoplastic drugs has been limited because oflow therapeutic index and lack of efficacy in humans. Improvement in efficacy ofnew anticancer drugs has been attempted by manipulating their pharmacokineticproperties. Four inter-related factors, which determine the pharmacokineticbehavior of a drug include absorption, distribution, metabolism and excretion.The drug-metabolizing enzymes have been classified in two major groups: phase Iand phase II enzymes. Phase I enzymes comprise the oxidases, dehydrogenases,deaminases, hydrolases. Phase II enzymes include primarily UDPglucuronosyltransferases(UGTs), glutathionetransferases (GSTs), sulfotransferases(SULTs), N-acetyl transferases (NATs), methyltransferases and aminoacidtransferases that conjugate products of phase I reactions and parent compoundswith appropriate functional groups to generate more water soluble compoundswhich are more readily eliminated. The importance of these enzymes in themetabolism of specific drugs varies according to the chemical nature of the drug,Drug metabolism is modulated by factors that change among species and evenamong individuals in a population. Such factors can be environmental or geneticin origin, and influence how a drug is metabolized and to what extent. An awarenessof these variables is invaluable when the safety and efficacy of new anticancerdrugs are evaluated
