Pharmacokinetic study of small molecule inhibitor SYHA1809 in Beagle dogs
- VernacularTitle:小分子抑制剂SYHA1809在比格犬体内的药动学研究
- Author:
Xiaolin LIU
1
,
2
;
Hanyu YANG
2
;
Xiaoyan WANG
2
;
Kai KANG
1
,
2
;
Min LIANG
2
Author Information
1. College of Pharmacy，Hebei Medical University，Shijiazhuang 050011，China
2. CSPC Zhongqi Pharmaceutical （Shijiazhuang） Co.，Ltd.，Shijiazhuang 050035，China
- Publication Type:Journal Article
- Keywords:
small molecule inhibitor;
SYHA1809;
LC-MS/MS;
pharmacokinetics
- From:
China Pharmacy
2023;34(17):2085-2089
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the pharmacokinetics of small molecule inhibitor SYHA1809 in Beagle dogs. METHODS LC-MS/MS method was adopted. Beagle dogs were randomly divided into single intravenous administration group （3.75 mg/kg）， single low-dose intragastric administration group （3.75 mg/kg）， single medium-dose intragastric administration group （7.5 mg/kg）， single high-dose intragastric administration group （15 mg/kg） and multiple intragastric administration group （7.5 mg/kg， once a day， for 7 consecutive days）， with 6 dogs in each group， half male and half female. The plasma samples of Beagle dogs were collected in each group according to the set time point， and underwent LC-MS/MS quantitative analysis after preprocessing. The pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.0 software using obtained data. RESULTS After intravenous injection， CL of SYHA1809 in Beagle dogs was （2.70±0.48） mL/（min·kg）， steady-state distribution volume was 0.757 L/kg， and t1/2 was （3.35±1.36） h； after single intragastric administration of low-dose， medium-dose and high-dose of SYHA1809， average tmax was （0.53±0.02） h， and the blood drug concentration increased with the increase of dose； after single intragastric administration of 3.75 mg/kg SYHA1809， the absolute bioavailability was 83.5%； within the dose range of 3.75-15 mg/kg， the increase in cmax and AUC of SYHA1809 was positively correlated with the dose； after intragastric administration of 7.5 mg/kg SYHA1809 for 7 consecutive days， the pharmacokinetic parameters of SYHA1809 were comparable to those of a single intragastric administration of the same dose， with no statistically significant difference （P＞0.05）. CONCLUSIONS SYHA1809 is absorbed rapidly in Beagle dogs， shows the dose-dependent blood concentration， high bioavailability， no obvious accumulation after multiple intragastric administration， and good pharmacokinetic behavior.
