Preliminary study on pharmacokinetics of DL0805-1:a novel Rho kinase inhibitor in rats
10.3969/j.issn.1001-1978.2014.08.027
- VernacularTitle:新型Rho激酶抑制剂DL0805-1大鼠体内药代动力学初步研究
- Author:
Yujie WU
;
Subo WANG
;
Tianyi YUAN
;
Renze LI
;
Xiaozhen JIAO
;
Ping XIE
;
Lianhua FANG
;
Guanhua DU
- Publication Type:Journal Article
- Keywords:
DL0805-1;
indazoles;
Rho kinase;
HPLC;
plasma concentration;
pharmacokinetics
- From:
Chinese Pharmacological Bulletin
2014;(8):1171-1174
- CountryChina
- Language:Chinese
-
Abstract:
Aim ToestablishthemethodofHighper-formance liquid chromatography ( HPLC ) for detecting plasma concentration of indazole compound DL0805-1 , a Rho kinase inhibitor, and to investigate its pharma-cokinetics in rats with intravenous injection. Methods ThedetectingsystemwasAgilent1200-DAD;chro-matographic column was Agilent TC-C18 ( 4. 6 mm × 250 mm, 5 μm); the ultraviolet detection wavelength was 235 nm; the column temperature was 35 ℃; the flow rate was 1 ml·min-1;the mobile phase was ace-tonitrile-0. 05% H3 PO4 gradient elute. Rat blood sam-ples were collected at different intervals after intrave-nous injection of a single dose of DL0805-1 , and the concentration of DL0805-1 in rat plasma were deter-mined by HPLC method for estimating pharmacokinetic parameters.Results Afterintravenousinjectionof DL0805-1 in rats, prototype and its metabolite were detected in plasma. T1/2 of DL0805-1=(2. 34 ± 1. 42) h, Cmax=(3. 51 ± 0. 44) mg·L-1, T1/2 of metabolite of DL0805-1 = ( 1. 27 ± 0. 45 ) h, Cmax = ( 3. 55 ± 0.22)mg·L-1.Conclusion Theseresultssuggest that DL0805-1 may be metabolized into another sub-stance in vivo and play biological functions. The meth-od is sensitive, simple, and accurate, and can be used for the determination of DL0805-1 in rat plasma and pharmacokinetic studies.
