Cost-utility analysis of pertuzumab combined with trastuzumab and docetaxel in first-line treatment of HER 2- positive metastatic breast cancer
- VernacularTitle:帕妥珠单抗联合曲妥珠单抗、多西他赛一线治疗HER2阳性转移性乳腺癌的成本-效用分析
- Author:
Caifeng JIA
1
;
Sen ZHANG
2
;
Hao XU
3
;
Sainan LI
4
;
Mingxia WANG
4
Author Information
1. Dept. of Clinical Pharmacology，the Fourth Hospital of Hebei Medical University，Shijiazhuang 050011，China
2. Dept. of Pharmacy，the Fourth Hospital of Hebei Medical University，Shijiazhuang 050011，China
3. Dept. of Medical Insurance，the Fourth Hospital of Hebei Medical University，Shijiazhuang 050011，China
4. Breast Center，the Fourth Hospital of Hebei Medical University，Shijiazhuang 050011，China
- Publication Type:Journal Article
- Keywords:
Euphorbia fischeriana;
diterpenoids;
ultra-high performance liquid chromatography-quadrupole time-of-flight mass
- From:
China Pharmacy
2022;33(4):481-486
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the metabolites of four diterpenoids of Euphorbia fischeriana in liver microsomes of rats and to investigate its metabolic regularity. METHODS In vitro incubation system of liver microsomes of rats was built. The jolkinolide A，jolkinolide B ，17-hydroxyl jolkinolide A and 17-hydroxyl jolkinolide B were added into incubation system of liver microsomes in rats activated by reduced nicotinamide adenine dinucleotide phosphate ，incubated at 37 ℃ for 30 min，and then terminated the reaction with acetonitrile. Taking the negative group （adding acetonitrile firstly and then starting incubation for 30 min）as the reference，the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used ；Anaylyst®TF 1.7.1、PeakView® 2.2，MetabolitePilot 1.5 and MasterView 1.2 software were used to speculate and identify the fragmentation law of mass spectrometry and metabolites. RESULTS Four diterpenoids were easy to lose neutral fragments such as H 2O and CO in secondary mass spectrometry. Jolkinolide A and 17-hydroxyl jolkinolide A showed similar metabolism pathway ，including dihydroxylation，dehydrogenation，and monohydroxylation ；six and five metabolites were identified respectively. Jolkinolide B and 17-hydroxyl jolkinolide B showed similar metabolism pathway ，including monohydroxylation ，hydration and isomerization. Five metabolites were identified. CONCLUSIONS Both jolkinolide A and 17-hydroxyl jolkinolide A produce the metabolites of hydroxylation and dehydrogenation in liver microsomes of rats ；both jolkinolide B and 17-hydroxyl jolkinolide B produce the metabolites of hydroxylation ，hydration and isomerization in liver microsomes of rats. The metabolites of four diterpenoids are phase Ⅰ metabolites.
