Clinical pharmacology of novel anticancer drug formulations

摘要: Studies outlined in this thesis describe the impact of drug formulations on pharmacology anticancer drugs. It consists four parts and starts with a review describing mechanisms low oral bioavailability anti-cancer drugs strategies for improvement bioavailability. The majority new are pharmaceutical formulations, consisting chemical entities, like molecular targeted agents novel variants existing development is, however, often hampered by variable Since most have narrow therapeutic window dosed at or close to maximum tolerated dose, wide variability can negative treatment outcome. extent depends many factors, including release from dosage form, drug’s stability gastro-intestinal tract, factors affecting dissolution, rate passage through gut wall pre-systemic metabolism liver. There several reduce overcome these limitations. First, adjustment formulation physicochemical characteristics improve dissolution absorption. Second, pharmacological interventions combining inhibitors transporter proteins and/or metabolizing enzymes physiological endogenous Third, modification synthesis derivative, salt form prodrug could enhance improving absorption bypassing limitations. In three other thesis, applied docetaxel, paclitaxel gemcitabine. These documented significant anti-tumor activity already use as first second line malignancies. Despite their proven activity, registered mode administration be responsible severe side effects, lead suboptimal dosing schedules. results show that an used further forms gemcitabine, but also relevant