# P-1243. Contezolid Tablets for Central Nervous System Tuberculosis in Adult Patients: pharmacokinetic and blood-brain barrier penetration

## TL;DR

Contezolid, a new antibiotic, was tested for its ability to reach the brain in patients with central nervous system tuberculosis.

## Contribution

This study is the first to evaluate the pharmacokinetics and blood-brain barrier penetration of contezolid in patients with CNS TB.

## Key findings

- Contezolid showed moderate penetration into cerebrospinal fluid but with significantly lower concentrations than in plasma.
- The drug's elimination was slower in cerebrospinal fluid compared to plasma.
- The study provides pharmacokinetic parameters of contezolid in both plasma and cerebrospinal fluid at steady-state.

## Abstract

Central nervous system tuberculosis (CNS TB), including tuberculous meningitis, is a life-threatening condition with high mortality rates [1]. Contezolid, a next-generation oxazolidinone antibiotic, has shown comparable efficacy to linezolid but with a significantly improved safety profile [2]. This exploratory study evaluated the pharmacokinetics (PK), and blood-brain barrier penetration of contezolid tablets in seven adult patients with CNS TB.Figure 1Concentration-time curves of contezolid in plasma and CSF at steady-stateFigure 2Contezolid CSF plasma concentration ratio

Concentration-time curves of contezolid in plasma and CSF at steady-state

Contezolid CSF plasma concentration ratio

Participants received a standardized anti-TB regimen, which includes rifampin: 10 mg/kg/day (maximum 600 mg), isoniazid: 5 mg/kg/day (maximum 600 mg), pyrazinamide: 30 mg/kg/day (maximum 2 g), levofloxacin: 500 mg/day, and dexamethasone and mannitol for adjunctive therapy. In addition to this regimen, contezolid tablets were administered at a dose of 800mg every 12 hours. Blood and cerebrospinal fluid (CSF) samples were collected prior to the first dose and at day 8 for PK assessments..Drug concentrations were measured by a validated liquid chromatography tandem mass spectrometry method. The steady-state PK parameters of contezolid in plasma and CSF were calculated using a noncompartmental model method. The blood-brain barrier penetration of contezolid was evaluated by the ratio of CSF to plasma drug concentration and exposure.

At steady-state, the plasma AUC0-12,ss and AUC0-∞,ss were 107.77±55.64 mg·h/L and 118.00±60.21 mg·h/L, whereas the CSF values were 11.40±3.14 mg·h/L and 16.62±12.24 mg·h/L, with penetration rates of 10.58% and 14.08%, respectively. The Tmax,ss in plasma and CSF were 3 h (1.5–6 h) and 6 h (3–9 h), and the CSF to plasma drug concentration ratio increased with time, indicating delayed drug entry into the CSF. The T1/2,ss in plasma and CSF were 2.49 h (1.17–4.54 h) and 3.18 h (1.39–10.42 h), suggesting slower elimination in CSF. The plasma clearance (CLss_F) and volume of distribution (Vss_F) were 9.00±3.86 L/h and 32.61±13.85 L, respectively.

Contezolid demonstrated moderate CSF penetration, but its CSF concentrations were markedly lower than plasma levels, indicating restricted distribution across the blood-brain barrier.

All Authors: No reported disclosures