Effects of rifampicin pretreatment on linezolid pharmacokinetics
10.13699/j.cnki.1001-6821.2024.10.021
- VernacularTitle:利福平预处理对利奈唑胺药代动力学的影响
- Author:
Yong-Cheng XU
1
;
Xiao-Xia YU
;
Ying WANG
;
Wei-Bin XIAO
;
Chen YANG
;
Bo JI
Author Information
1. 广东药科大学医药化工学院,广东广州 510000
- Keywords:
linezolid;
rifampicin;
high performance liquid mass spectrometry;
pharmacokinetics;
lung tissue
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(10):1492-1496
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of rifampicin on the pharmacokinetics of linezolid in mice and provide pharmacokinetic evidence for the formulation of safe drugs for clinical use of pulmonary tuberculosis.Methods Fifty male KM mice were randomly divided into 2 groups:Control group,rifampicin group;the control group was given 15 mg·kg-1 linezolid;the rifampicin group was given 100 mg·mL-1 rifampicin,continuous administration for 7 days,followed by gavage,administration of 15 mg·kg-1 linezolid;blood and lung tissue were collected from mouse at different time points after administration.High performance liquid mass spectrometry(LC-MS/MS)was used to determine plasma concentration of linezolid and compared the pharmacokinetics between groups.Pharmacokinetic parameters were calculated using DAS 2.0 software.Results Main pharmacokinetic parameters of plasma linezolid in control group,rifampicin group were as follows:AUC0_t were(23.88±1.16)and(19.06±2.56)pg·mL-1·h,respectively;t1/2 were((1.15±0.11)and(1.11±0.10)h,respectively;Cmax were(9.93±0.46)and(7.74±1.17)μg·mL-1,respectively.The main pharmacokinetic parameters of the lungs in the control group and the rifampicin group were as follows:AUC0_t were(18.76±4.29)and(14.90±1.52)μg·mL-1·h,respectively;t1/2 were(1.94±0.50)and(1.44±0.07)h,respectively;Cmax were(8.28±2.67)and(6.82±1.57)μg·mL-1,respectively.AUC0_t and Cmax in plasma and AUC0_t in lung tissue of control group were significantly different from those of rifampicin group(all P＜0.05).Conclusion After the combination of rifampicin,linezolid plasma and lung tissue exposure decreased significantly,and attention should be paid to monitoring linezolid trough concentration when the two drugs were combined to avoid treatment failure caused by low effective concentration.
