[Chemical modification of anticancer agents from viewpoints of their pharmacokinetics]

Many derivatives modifying chemical structures have been synthesized from several drugs. These include following antibiotics: adriamycin; 4'-epiadriamycin, THP-adriamycin, demethoxy-daunomycin, aclacinomycin, mitomycin C; 7N-(p-hydroxyphenyl)-mitomycin C, bleomycin; peplomycin, oilbleomycin, neocarzinostatin; macromomycin, and following antimetabolites: 5-FU; tegafur, HCFU, 5'-DFUR, phthalidyl-5-FU, FUdR; TK-117, FF-705, Ara-C; behenoyl-Ara-C. Most derivatives of antibiotics were a low toxic type and showed a shorter distribution time and a rapid inactivation, except peplomycin and 4-demethoxy-daunomycin. Antimetabolite derivatives were a masked type. They were activated to 5-FU, FUdR or Ara-C and persisted for a long time in the body. The mode of activation and KADME varied each other. By considering these pharmacokinetic behaviors, a suitable method of administration should be established.