Pharmacokinetic characteristics of 14CCHMFL-FLT3-122 in rats
10.16438/j.0513-4870.2018-1109
- VernacularTitle:[14C]CHMFL-FLT3-122在大鼠体内的药代动力学研究
- Author:
Dong-yang LI
1
,
2
;
Xiao WANG
3
;
Xiao-rong LU
3
;
Jin YANG
1
;
Hong-zhang SUN
4
Author Information
1. China Pharmaceutical University, Nanjing 210009, China
2. Hefei Cosource Pharmaceuticals Inc., Hefei 230031, China
3. Hefei Blooming Drug Safety Evaluation, Co. LTD., Hefei 230031, China
4. Hefei Cosource Pharmaceuticals Inc., Hefei 230031, China
- Publication Type:Research Article
- Keywords:
CHMFL-FLT3-122;
acute myelocytic leukemia;
italic>in vivo metabolism;
ADME;
radiolabelling
- From:
Acta Pharmaceutica Sinica
2019;54(4):714-719
- CountryChina
- Language:Chinese
-
Abstract:
The study was conducted to characterize the pharmacokinetics, distribution, metabolism and excretion of CHMFL-FLT3-122 after a single oral dose of 50 mg·kg-1 [14C] labeled CHMFL-FLT3-122 in rats. Isotope tracing techniques were used to analyze drug concentration and identify the distribution of drugs in tissues and metabolites in biological samples. The experiments were approved by the Animal Ethics Committee of XenoBiotic Laboratories-China, Inc. The absolute bioavailability in male and female rats were 45.83% and 50.92% respectively. The parent drug and its metabolites were extensively distributed in the stomach, intestine, liver and lung, and were eliminated completely in 48 h. The majority of radioactivity was excreted through the feces at 92.34% of the dose with a small fraction through urine at 3.99% of the dose. The parent drug was the most significant circulating component, representing 49.23% and 70.65% over the 0-48 h collection time interval in the plasma of male and female. Two major metabolites, M553 (sulfate conjugate) and M457 (N-dealkyl product), were identified in plasma. Metabolites of CHMFL-FLT3-122, including ten phase I and four phase II metabolites, were identified. The metabolic pathways of CHMFL-FLT3-122 were proposed as N-dealkylation, oxidation, amide hydrolysis, sulfate conjugation, and glucuronic conjugation.
