Penetration of linezolid and tedizolid in cerebrospinal fluid of mouse and impact of blood–brain barrier disruption
Abstract 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 l...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.70100 |
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| author | Marin Lahouati Mélanie Oudart Philippe Alzieu Candice Chapouly Antoine Petitcollin Fabien Xuereb |
| author_facet | Marin Lahouati Mélanie Oudart Philippe Alzieu Candice Chapouly Antoine Petitcollin Fabien Xuereb |
| author_sort | Marin Lahouati |
| collection | DOAJ |
| description | Abstract 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. The impact of blood–brain barrier disruption on linezolid and tedizolid (antibiotics that may be alternatives to treat nosocomial meningitis) penetration in cerebrospinal fluid (CSF) remains unknown. The aim of this study is to evaluate the impact of blood brain barrier disruption on CSF penetration of linezolid and tedizolid. Female C57BI/6 J mice were used. Blood–brain barrier disruption was induced by an intraperitoneal administration of lipopolysaccharide. Linezolid (40 mg/kg) or tedizolid‐phosphate (20 mg/kg) were injected intraperitoneally. All the plasma and CSF samples were analyzed with a validated UPLC‐MS/MS method. Pharmacokinetic parameters were calculated using a non‐compartmental approach based on the free drug concentration. The penetration ratio from the plasma into the CSF was calculated by the AUC0‐8h (Area Under Curve) ratio (AUC0‐8hCSF/AUC0‐8hplasma). Linezolid penetration ratio was 46.5% in control group and 46.1% in lipopolysaccharide group. Concerning tedizolid, penetration ratio was 5.5% in control group and 15.5% in lipopolysaccharide group. In conclusion, CSF penetration of linezolid is not impacted by blood–brain barrier disruption, unlike tedizolid, whose penetration ratio increased. |
| format | Article |
| id | doaj-art-186d352f1b6b4f1297df8d29246562ab |
| institution | Kabale University |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj-art-186d352f1b6b4f1297df8d29246562ab2025-01-24T08:17:46ZengWileyClinical and Translational Science1752-80541752-80622025-01-01181n/an/a10.1111/cts.70100Penetration of linezolid and tedizolid in cerebrospinal fluid of mouse and impact of blood–brain barrier disruptionMarin Lahouati0Mélanie Oudart1Philippe Alzieu2Candice Chapouly3Antoine Petitcollin4Fabien Xuereb5Service de Pharmacie Clinique CHU de Bordeaux, Hôpital Pellegrin Bordeaux FranceService de Pharmacie Clinique CHU de Bordeaux, Hôpital Pellegrin Bordeaux FranceINSERM U1034, Biologie des Maladies Cardiovasculaires Université de Bordeaux Pessac FranceINSERM U1034, Biologie des Maladies Cardiovasculaires Université de Bordeaux Pessac FranceLaboratoire de Pharmaco‐Toxicologie Biologique et Médico‐Légale CH Tarbes‐Lourdes Tarbes FranceService de Pharmacie Clinique CHU de Bordeaux, Hôpital Pellegrin Bordeaux FranceAbstract 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. The impact of blood–brain barrier disruption on linezolid and tedizolid (antibiotics that may be alternatives to treat nosocomial meningitis) penetration in cerebrospinal fluid (CSF) remains unknown. The aim of this study is to evaluate the impact of blood brain barrier disruption on CSF penetration of linezolid and tedizolid. Female C57BI/6 J mice were used. Blood–brain barrier disruption was induced by an intraperitoneal administration of lipopolysaccharide. Linezolid (40 mg/kg) or tedizolid‐phosphate (20 mg/kg) were injected intraperitoneally. All the plasma and CSF samples were analyzed with a validated UPLC‐MS/MS method. Pharmacokinetic parameters were calculated using a non‐compartmental approach based on the free drug concentration. The penetration ratio from the plasma into the CSF was calculated by the AUC0‐8h (Area Under Curve) ratio (AUC0‐8hCSF/AUC0‐8hplasma). Linezolid penetration ratio was 46.5% in control group and 46.1% in lipopolysaccharide group. Concerning tedizolid, penetration ratio was 5.5% in control group and 15.5% in lipopolysaccharide group. In conclusion, CSF penetration of linezolid is not impacted by blood–brain barrier disruption, unlike tedizolid, whose penetration ratio increased.https://doi.org/10.1111/cts.70100 |
| spellingShingle | Marin Lahouati Mélanie Oudart Philippe Alzieu Candice Chapouly Antoine Petitcollin Fabien Xuereb Penetration of linezolid and tedizolid in cerebrospinal fluid of mouse and impact of blood–brain barrier disruption Clinical and Translational Science |
| title | Penetration of linezolid and tedizolid in cerebrospinal fluid of mouse and impact of blood–brain barrier disruption |
| title_full | Penetration of linezolid and tedizolid in cerebrospinal fluid of mouse and impact of blood–brain barrier disruption |
| title_fullStr | Penetration of linezolid and tedizolid in cerebrospinal fluid of mouse and impact of blood–brain barrier disruption |
| title_full_unstemmed | Penetration of linezolid and tedizolid in cerebrospinal fluid of mouse and impact of blood–brain barrier disruption |
| title_short | Penetration of linezolid and tedizolid in cerebrospinal fluid of mouse and impact of blood–brain barrier disruption |
| title_sort | penetration of linezolid and tedizolid in cerebrospinal fluid of mouse and impact of blood brain barrier disruption |
| url | https://doi.org/10.1111/cts.70100 |
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