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Pharmacokinetics, tissue distribution and excretion of ACT001 in Sprague-Dawley rats and metabolism of ACT001
- Source :
- Journal of Chromatography B. 1104:29-39
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- This study investigated pharmacokinetics, tissue distribution and excretion of ACT001 in Sprague-Dawley rats. Stability study and metabolism study of ACT001 are conducted. The absolute bioavailability of ACT001 is 50.82%. ACT001 has no accumulation effect and displayed wide tissue distribution. ACT001 can be rapidly distributed to tissues after oral administration and can diffuse through the blood-brain barrier. The total cumulative excretion of ACT001 in feces, urine and bile were found to be 0.05, 3.42 and 0.012%, respectively. UPLC/ESI-QTOF-MS coupled with MetaboLynx XS software was utilized to detect the metabolites of ACT001 in vitro. Five metabolites (M1, M2, M3, M4 and M5) were detected. M2 wasn't discovered in human liver microsome samples and bile samples. M1 and M2 weren't discovered in rat plasma and human plasma. M3, M4 and M5 weren't discovered in bile samples. M5 is an active metabolite named micheliolide (MCL). There is no significant difference in half-life, type of identified metabolites and the amount of each metabolites between using rat plasma and human plasma. Owing to the species differences of hepatomicrosome enzymes, significant differences were shown in half-life, type of identified metabolites and the amount of each metabolites between using rat liver microsome and human liver microsome.
- Subjects :
- Clinical Biochemistry
Administration, Oral
Urine
Pharmacology
030226 pharmacology & pharmacy
01 natural sciences
Biochemistry
Analytical Chemistry
Rats, Sprague-Dawley
Excretion
Sesquiterpenes, Guaiane
03 medical and health sciences
0302 clinical medicine
Drug Stability
Pharmacokinetics
Limit of Detection
Oral administration
Animals
Tissue Distribution
Active metabolite
Chromatography
Chemistry
010401 analytical chemistry
Reproducibility of Results
Cell Biology
General Medicine
Metabolism
In vitro
Rats
0104 chemical sciences
Linear Models
Microsome
Subjects
Details
- ISSN :
- 15700232
- Volume :
- 1104
- Database :
- OpenAIRE
- Journal :
- Journal of Chromatography B
- Accession number :
- edsair.doi.dedup.....291e594913be60a42623a4c3e570209f