Phase Ⅰ Trial Of Human Tolerability And Pharmacokinetics To Gambogic Acid

objective: the current study was designed to observed the human tolerability and pharmacokinetics profiles and to determine the maximal tolerated dose(MTD) dose-limiting toxicity(DLT) to gambogic acid intravenously. The safe and effective regimen would be recommend for the Phase II clinical trial . Methods: the study was divided into two steps: Phase I trial of human tolerability and pharmacokinetics to gambogic acid with single medication and Phase I trial of human tolerability and pharmacokinetics to gambogic acid succeccive medication study, the clinical trial with single medication was performed by modified Fibonacci series. The starting dose was 10mg/m~2, cohorts of three patients were treated at each dose level, if severe toxicity had not occurred, the dose escalated to the next level till to the dose-limiting toxicity(DLT). Serium sample were obtained before administration and up to 48 hours after the administration for pharmacokinetics study. The dose levels of clinical trial with succeccive medication were 10mg/m~2 25mg/m~2 35mg/m~2 45mg/m~2 60mg/m~2 respectively. Medication regimens were Qd×5 2/w×2 weeks Qd×7 Qod×7 Qd×5; safety and respone were evaluated in one month. Serium sample were obtained for pharmacokinetics study. Results : 15 patients were enrolled in Phase I trial of human tolerability and pharmacokinetics to gambogic acid with single medication ,the dose levels were 10mg/m~2 20mg/m~2 35mg/m~2 55mg/m~2 70mg/m~2 respectively, In the fifth dose level(70mg/m~2), grade 4 going up of ALT...