Your browser doesn't support javascript.
loading
Pharmacokinetics and sedation of sufentanil and dexmedetomidine combination in rats / 中国药理学与毒理学杂志
Chinese Journal of Pharmacology and Toxicology ; (6): 63-69, 2019.
Article in Chinese | WPRIM | ID: wpr-857577
ABSTRACT
OBJECTIVE To evaluate plasma pharmacokinetics, distribution of target organs, sedative effect and respiratory depression of sufentanil (SFTN), and dexmedetomidine (DEM) in rats, and to explore the potential drug-drug interactions between the two drugsMETHODS  Rats were intravenously injected with SFTN 20.0 μg•kg-1, DEM 25.2 μg•kg-1 and SFTN+DEM (SFTN 20.0 μg•kg-1, DEM 25.2 μg•kg-1), respectively. Plasma samples were taken at different time points (2, 5, 15, 30 min and 1, 2, 4, 6, 8 h) to determine the concentrations of SFTN and DEM using the liquid chromatography-mass spectrometry (LC-MS/MS) quantitative method established in this study. The same method was used to determine the concentrations of SFTN and DEM in plasma and brain samples taken at different time points (5, 15, 30, 60 and 120 min). Pharmacokinetic parameters were obtained by noncompartmental analysis performed using Phoenix WinNonlin 7.0 (Pharsight, California). The duration of drug-induced loss of right reflex (LORR) and respiratory function were also measured using instrument monitoring. RESULTS  An LC-MS/MS method for quantitative analysis of plasma SFTN and DEM was established and validated. The Cmax,;t1/2, and Cl ;of SFTN in SFTN group were (22.2±2.6) ug•L-1, (2.13±0.69) h and (2288±446) mL•h-1•kg-1, respectively, compared with (15.9±9.4) μg•L-1, (1.22±0.13) h and (3565±743) mL•h-1 •kg-1 in SFTN+DEM group. The Cmax, t1/2, and Cl of DEM in DEM group were (14.0±8.9) μg•L-1, (1.21±0.15) h and (4235±752) mL•h-1•kg-1, compared with (9.4±3.5) μg•L-1, (1.08±0.26) h and (4796±744) mL•h-1•kg-1 in SFTN+DEM group. The Cmax ratio of SFTN in brain and plasma of SFTN+DEM group was 0.49, which was 1.3-fold that of SFTN group (0.45). The Cmax ratio of DEM in brain and plasma of SFTN + DEM group was 16.9, which was 12-fold that of DEM group (1.42). The duration of LORR of SFTN, DEM, and SFTN+DEM groups was 370±13, 41±5 and (104±24) min, respectively, and that of SFTN+DEM group was more significantly extended than those in SFTN and DEM groups (P<0.01). Respiratory depression of SFTN+DEM group was not further aggravated compared with SFTN group, but the duration of inhibition was extended (P<0.05, P<0.01). CONCLUSION  The combination of SFTN and DEM can cause drug-drug interactions, which may promote the sedation and prolong the respiratory depression by increasing the exposure level of DEM brain tissue. In clinical application, attention should be paid to the possible drug-drug interactions or adverse reactions caused by the combination of these two drugs.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Pharmacology and Toxicology Year: 2019 Type: Article

Similar

MEDLINE

...
LILACS

LIS

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Pharmacology and Toxicology Year: 2019 Type: Article