Pharmacokinetic study of small molecule inhibitor SYHA1809 in Beagle dogs

LIU Xiaolin; YANG Hanyu; WANG Xiaoyan; KANG Kai; LIANG Min

doi:10.6039/j.issn.1001-0408.2023.17.07

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Pharmacokinetic study of small molecule inhibitor SYHA1809 in Beagle dogs

更新时间：2023-09-14

- Pharmacokinetic study of small molecule inhibitor SYHA1809 in Beagle dogs
- ZHONGGUO YAOFANG Vol. 34, Issue 17, Pages: 2085-2089(2023)
- 作者机构：
  
  1.河北医科大学药学院，石家庄;050011
  2.石药中奇制药（石家庄）有限公司，石家庄　050035
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.17.07
  CLC： R969.1
- Published：15 September 2023，
  
  Received：13 February 2023，
  
  Revised：25 July 2023，
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刘晓琳,杨汉煜,王小彦等.小分子抑制剂SYHA1809在比格犬体内的药动学研究 ^Δ[J].中国药房,2023,34(17):2085-2089.

LIU Xiaolin,YANG Hanyu,WANG Xiaoyan,et al.Pharmacokinetic study of small molecule inhibitor SYHA1809 in Beagle dogs[J].ZHONGGUO YAOFANG,2023,34(17):2085-2089.
刘晓琳,杨汉煜,王小彦等.小分子抑制剂SYHA1809在比格犬体内的药动学研究 ^Δ[J].中国药房,2023,34(17):2085-2089. DOI： 10.6039/j.issn.1001-0408.2023.17.07.

LIU Xiaolin,YANG Hanyu,WANG Xiaoyan,et al.Pharmacokinetic study of small molecule inhibitor SYHA1809 in Beagle dogs[J].ZHONGGUO YAOFANG,2023,34(17):2085-2089. DOI： 10.6039/j.issn.1001-0408.2023.17.07.

摘要

目的

研究小分子抑制剂SYHA1809在比格犬体内的药动学。

方法

采用液相色谱-串联质谱（LC-MS/MS）法进行测定。将比格犬随机分为单次静脉给药组（3.75 mg/kg）、单次低剂量灌胃组（3.75 mg/kg）、单次中剂量灌胃组（7.5 mg/kg）、单次高剂量灌胃组（15 mg/kg）和多次灌胃组（7.5 mg/kg，每天1次，连续7 d），每组6只，雌雄各半。各组比格犬按照设定的时间点收集血浆样品，经预处理后进行LC-MS/MS定量分析，获得的数据采用Phoenix WinNonlin 8.0软件计算药动学参数。

结果

SYHA1809静脉注射给药后，在比格犬体内的CL为（2.70±0.48） mL/（min·kg），稳态分布体积为0.757 L/kg，

1/2

为（3.35±1.36） h；单次灌胃给予低、中、高剂量的SYHA1809后，其在比格犬体内的平均

max

为（0.53±0.02） h，血药浓度随给药剂量的增加而升高；单次灌胃给予3.75 mg/kg的SYHA1809后，绝对生物利用度为83.5%；在3.75～15 mg/kg剂量范围内，SYHA1809的

max

和AUC增加与剂量呈正相关；SYHA1809连续以7.5 mg/kg灌胃7 d后，与同剂量单次灌胃给药后的药动学参数相当，差异无统计学意义（

＞0.05）。

结论

SYHA1809在比格犬体内吸收迅速，血药浓度呈剂量依赖性，生物利用度高，多次灌胃给药后无明显蓄积，药动学行为良好。

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

1/2

was （3.35±1.36） h； after single intragastric administration of low-dose， medium-dose and high-dose of SYHA1809， average

max

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

max

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 （

＞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.

关键词

小分子抑制剂SYHA1809液相色谱-串联质谱法药动学

Keywords

SYHA1809LC-MS/MSpharmacokinetics

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