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.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.yrtph.2019.104420 | DOI Listing |
Clin Transl Sci
January 2025
Service de Pharmacie Clinique, CHU de Bordeaux, Hôpital Pellegrin, Bordeaux, France.
Penetration of antimicrobial treatments into the cerebrospinal fluid is essential to successfully treat infections of the central nervous system. This penetration is hindered by different barriers, including the blood-brain barrier, which is the most impermeable. However, inflammation may lead to structural alterations of these barriers, modifying their permeability.
View Article and Find Full Text PDFJ Glob Antimicrob Resist
November 2024
Department of Hematology, Tianjin First Central Hospital, Tianjin, PR China.
Objective: The objective of this study was to investigate the cumulative fraction of response of various dosage regimens of tedizolid phosphate against Staphylococcus aureus and Streptococcus pneumoniae in children, adolescents, and adults.
Methods: Monte Carlo simulations were performed using previously published pharmacokinetic parameters and pharmacodynamic data to evaluate the efficacy of the simulated dosage strategies in terms of area under the concentration-time curve/minimum inhibitory concentration targets of tedizolid.
Results: According to the results of the Monte Carlo simulations, currently approved dosage regimens of tedizolid phosphate were effective in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by methicillin-susceptible S.
Int J Pharm
November 2024
Department of Biology, Science Faculty, Ege University, 35100 İzmir, Turkey; Laboratory Animals Research Center, Ege University, 35100 İzmir, Turkey.
Int Immunopharmacol
June 2024
School of Basic Medicine, Dali University, Dali 671000, Yunnan, China. Electronic address:
J Assoc Res Otolaryngol
June 2024
Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, 250117, China.
Purpose: Cisplatin is a low-cost clinical anti-tumor drug widely used to treat solid tumors. However, its use could damage cochlear hair cells, leading to irreversible hearing loss. Currently, there appears one drug approved in clinic only used for reducing ototoxicity associated with cisplatin in pediatric patients, which needs to further explore other candidate drugs.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!