Comparative pharmacokinetics of tedizolid in rat plasma and cerebrospinal fluid.

Regul Toxicol Pharmacol

College of Pharmaceutical Science, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang district, Hangzhou, 310053, China; Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, China. Electronic address:

Published: October 2019

To investigate the possibility of tedizolid phosphate's application in the treatment of intracranial infection, a preclinical comparative pharmacokinetic study was designed. Based on the assumption that the classic efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may participate in the transportation of TDZ, two groups of rats were intravenously administered 6 mg/kg tedizolid phosphate alone or 6 mg/kg tedizolid phosphate combined with 1 mg/kg elacridar which was an inhibitor of P-gp and BCRP. Plasma and cerebrospinal fluid samples were collected according to a pharmacokinetic schedule. All the plasma and cerebrospinal fluid samples were assessed with a validated LC-MS/MS method. The penetration ratio of tedizolid from the blood to cerebrospinal fluid was calculated, and a comparison of the penetration ratios between the two groups was made. The mean C of tedizolid in the CSF in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 154 ng/mL and 300 ng/mL, respectively, and the mean penetration ratio of tedizolid in the tedizolid phosphate group and the tedizolid phosphate combined with elacridar group was 2.16% and 3.53%, respectively. The relatively high C in the CSF proved the possibility of tedizolid phosphate's application in the treatment of intracranial infection, and the higher penetration ratios, C and AUC of the rats in co-administered elacridar group than those in the single-administration group indicated that the transporters P-gp and BCRP might be involved in the transportation of tedizolid.

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http://dx.doi.org/10.1016/j.yrtph.2019.104420DOI Listing

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