OBJECTIVE:Comparing
pharmacokinetic and toxicity of 10- hydroxycamptothecin on different intravenous administrion. METHODS:Doseinitiated
at 12mg.m2,was solved in 0.9%Ncl 1OOml, given as follows:(a)30min constant infusion for 5consecutive days;(b)4h constant infusion for 10 consecutive days; (c)8h constant infusion for 10 consecutive days. Patients were evaluated for response after two weeks. Heparinized blood samples(2m1) were collected on the day 1,5,10 day, immediately predose (time 0), then postinfusion at 0,15,30 minutes, and 1,2,4,6,8,12 hours.
Pharmacokinetic analysis was performed in 18 patients using a validated high-performance liquid chromatographic assay and 3p97. RESULTS: Infusion time increasing from 30mm to 8h, the main adverse intensity and incidence rate decreased accordingly. (a)30min constant infusion, 4/6 patients
experienced I- III grade neutorpenia, 1/6 had diarrhea and 3/6had nausea and vomiting. (b)4h infusion, 2/6 experienced I-IT grade neutropenia and nausea and vomiting.C:8h infusion, no patient experienced any toxicity. A two-compartment model was used to fit the plasma concentration-time curve;with a terminal elimination half-life(t1/2,β) of 1.03 ±0.58h 3 82 + 0.96h, 3.41 ±1.05h respectively. Distributon volumes (Vd) is 5.54 ±5.2L 18.1 ± 5.7L. 25.4 ±8.3L respectively. CONCLUSION:Infusion time rising from 30mm to 4h, t1/2,β and Vdincrease accordingly,but increasing to 8h, t1/2,β and Vd do not increasing accordingly with C decreasing. The incidence of toxicity occuring in 4h, 8h is less frequent than in 30mm.