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Population pharmacokinetics of levornidazole in healthy subjects and patients, and sequential dosing regimen proposal using pharmacokinetic/pharmacodynamic analysis.
- Source :
-
International Journal of Antimicrobial Agents . Apr2023, Vol. 61 Issue 4, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- • The first population pharmacokinetic model of levornidazole in Chinese subjects was developed. • Pharmacokinetic/pharmacodynamic analysis of four sequential dosing regimens was performed. • Body weight was identified as a significant covariate of levornidazole clearance. • 750 mg q24h was proposed for patients against Bacteroides spp. (minimum inhibitory concentration ≤1 mg/L). Although sequential treatment with levornidazole has been used for anaerobic infection in clinical practice, there is no evidence-based dosing regimen. This study aimed to evaluate the pharmacokinetics (PK) of levornidazole in healthy subjects and patients, and to propose an evidence-based sequential dosing regimen by pharmacokinetic/pharmacodynamic (PK/PD) analysis. A population PK model was built using the data of 116 Chinese subjects, including 88 healthy young subjects, 12 healthy elderly subjects, and 16 patients with intra-abdominal anaerobic infection. PK/PD analysis was performed combining the minimum inhibitory concentration (MIC) values of levornidazole against 375 anaerobic strains. Four sequential dosing regimens (500 mg q12h, 1000 mg loading dose followed by 500 mg q12h, 750 mg q24h, and 1000 mg q24h) were evaluated in terms of cumulative fraction of response (CFR) and probability of target attainment (PTA) by Monte Carlo simulation. The concentration data of levornidazole and its active metabolites were described adequately by two- and one-compartment models, respectively. Body weight was identified as a significant covariate of levornidazole clearance. Simulations showed that satisfactory PTA (>90%) was achieved for the four dosing regimens when MIC ≤1 mg/L. Considering the simulation results, patients' safety and compliance, levornidazole 750 mg intravenous infusion q24h for 2 days followed by 750 mg oral dose q24h for 5 days was optimal for Bacteroides spp. with an identified MIC ≤1 mg/L. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09248579
- Volume :
- 61
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- International Journal of Antimicrobial Agents
- Publication Type :
- Academic Journal
- Accession number :
- 162760626
- Full Text :
- https://doi.org/10.1016/j.ijantimicag.2023.106754