Comparative pharmacokinetics of tedizolid in rat plasma and cerebrospinal fluid

Publication date: Available online 8 July 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Liqiang Gu, Munong Ma, Yuan Zhang, Lijiang Zhang, Sheng Zhang, Mincong Huang, Majuan Zhang, Yanfei Xin, Gaoli Zheng, Suhong ChengAbstractTo 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 Cmax 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 hi...

Source: Regulatory Toxicology and Pharmacology - July 9, 2019 Category: Toxicology Source Type: research