| Objective:To evaluate the tolerability and safety of 9-nitrocamptothecin and it's anticancer effect on malignant tumor patients.Method:The trail was designed from single dosage to successive medication,from low dose to high dose.single dosage:32 patients with malignant tumor were divided into four groups.1.0mg/m2,1.25mg/m2,1.5mg/m2,1.75mg/m2,2.0mg/m2.the tolerance and safety of 9-NC were assessed based on changes of blood and urine routine,serum chemistry, cruor function, electrocardiogram on the third and seven day after taking medicine.successive administration: 13 patients were divided into 3 groups, 9-NC was taken in a dose-escalation scheme 1.25mg/m2/d, 1.5mg/m2/d, 1.75mg/m2/d. daily for 3 weeks.The tolerance and laboratory examination was observed on the 3, 10, 17, 28day.The size of tumor was scanning by CT, detection the change of tumor marker and quality of life, evaluation the effect of anti-tumor. Results: In single dosage group, The main toxicities include nausea(28.1%), anemia(21.8%),leucopenia (15.6%), hematuria(12.5%), diarrhea(6.25%) etc. In successive administration group,There are thirteen patients can be evaluated. The side effect include fatigue3(23.0%), leukopenia 3(23.0%),nausea and vomit 3(23.0%), sour regurgitation2(15.3%) hematuria 1 ( 7.7% ),diarrhea 1 (7.7%) abnormal oftransaminasel (7.7%), The II degree nausea,vomit and myelosuppression emerge in 1.75mg/m2/d group. One patient with liver cancer who used 9-NC curative effect evaluation CR.Conelusions: The recommended Phase II doses for schedules single dosage and successive administration is 1.75 mg/m2 and 1.5 mg/m2/d,respectively. These studies suggest that 9-NC administered on this schedule have good tolerce and very low side-effect, oral administration is very ??convenience. Objective: Determination of 9-nitrocamptothecin in patient's plasma by high performance liquid chromatography,In order to understand the rule of absorption distribution metabolism and excretion of 9-NC.Indicate the t1/2.Method: single dosage: 18 patients with malignant tumor were divided into 3 groups. 1.25mg/m2,1.5mg/m2,1.75mg/m2.HPLC is used to test the plasma of patient before drug taken 15min and then 1,2,3,4,5,6,8,12,24,36h after drug taken.successive administration: 9 patients were divided into 3 groups,1.25mg/m2/d,1.5mg/m2/d,1.75mg/m2/d. daily for 3 weeks. HPLC is used to test the plasma of patient before drug taken 15rain and then 1,2,3,4,5,6,8,12,24,36,47.45,71.45,95.45,96.5,97,98,99,100,101,102,104,108,120,132,144h. Plasma samples were prepared based on a simple liquid—solid extraction,and separation through a Kromasil C18Column. The mobile phase for plasma samples is methanol phosphate solution (0.01 mol/l) (V/V48:52,PH=2.5) .respectively. The UV detector Was set at 370 nm.Results: A linear calibration curve of 9-nitrocamptothecin in plasma Cmax and AUC was obtained in single dosage group and in successive administration groupConclusions: the mean Tmax in single dosage group is 3.67h and T1/2 is 11.06h. HPLC is shown to be accurate and convenient, and suitable for pharmacokinetic studies of 9-nitrocamptothecin.
|
PDF Full Text Request