Effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats
- VernacularTitle:氯吡格雷对大鼠体内环泊酚药动学和药效学的影响
- Author:
Ming LU
1
;
Xiaoyu YIN
2
;
Wenli LI
1
;
Shan LI
1
;
Xiangchen LI
1
;
Zhiqing ZHANG
1
Author Information
1. Dept. of Pharmacy，the Second Hospital of Hebei Medical University，Shijiazhuang 050052，China
2. Dept. of Pharmacy，Hebei General Hospital，Shijiazhuang 050051，China
- Publication Type:Journal Article
- Keywords:
clopidogrel;
ciprofol;
drug-drug interactions;
pharmacokinetics;
pharmacodynamics
- From:
China Pharmacy
2025;36(2):179-184
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats. METHODS Eighteen male SD rats were randomly divided into control group， clopidogrel normal-dose group and clopidogrel high-dose group， with 6 rats in each group. Among them， rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage， respectively， and rats in the control group were given the same volume of 0.5% sodium carboxymethyl cellulose solution， once a day， for 14 consecutive days. Afterward， 2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2， 4， 8， 12， 16， 20， 30， 45 and 60 min after the end of the administration. During this period， the duration of the loss of righting reflex （LORR） in rats was counted. After the proteins were precipitated by acetonitrile， the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard， Symmetry C18 as the chromatographic column， and acetonitrile-0.01% ammonia solution containing 5 mmol/L ammonium acetate （gradient elution） as the mobile phase to detect the concentration of ciprofol in the plasma. The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software. RESULTS Compared with control group， area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly， while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups； the duration of LORR in rats was prolonged by 19.5% and 23.9%， with statistical difference （P＜0.05）. However， there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel （P＞0.05）. CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.
