We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pharmacokinetic and Pharmacodynamic Modeling Analysis of Delpazolid (LCB01‐0371) in Adult Patients with Pulmonary Tuberculosis.
- Authors
Lee, Sang Min; Choi, Seung Chan; Mun, Kyung Ran; Seo, Ji Young; Cho, Young Lag; Shim, Tae Sun; Lim, Hyeong‐Seok
- Abstract
Delpazolid (LCB01‐0371) is a novel oxazolidinone derivative with a good safety profile for treating gram‐positive pathogenic infections such as Mycobacterium abscessus, a highly pathogenic drug‐resistant Mycobacterium. In this study, we evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of delpazolid after 14 days of multiple oral administration, using data from adult patients with pulmonary tuberculosis. 800 mg once a day, 400 mg twice a day, 800 mg twice a day, and 1200 mg once a day delpazolid for 14 days were tested in 63 patients with pulmonary tuberculosis. For PK blood collection, inpatient and outpatient scheduling were separately implemented. Plasma concentrations of delpazolid were measured at visits 2, 4, 6, and 8 in outpatients, and four sparse blood samples were measured in inpatients. PD models were sequentially fitted using individual PK parameter estimates obtained from PK compartmental models. For PK modeling, 180 plasma concentrations of delpazolid from 56 patients were included. A two‐compartment mixed first‐ and zero‐order absorption model best described the time course of plasma concentration. For the PD model, 448 bacterial titer data from 60 patients were used. The time course of bacterial titers (log10 CFU/mL) was described by a model that consists of the growth and killing rate of bacteria with the sigmoid Emax model. The PK–PD simulation suggested that the bacterial titers are the lowest on the 800 mg bid regimen among the four, consistent with observed data, as all regimens substantially decrease. In the dose–response relationship, the effectiveness of delpazolid was suggested.
- Subjects
DRUG therapy for tuberculosis; BIOLOGICAL models; RESEARCH funding; ORAL drug administration; DESCRIPTIVE statistics; ANTITUBERCULAR agents; SIMULATION methods in education; DOSE-effect relationship in pharmacology; MASS spectrometry; DATA analysis software; CONFIDENCE intervals; PHARMACODYNAMICS; ADULTS
- Publication
Journal of Clinical Pharmacology, 2024, Vol 64, Issue 7, p849
- ISSN
0091-2700
- Publication type
Article
- DOI
10.1002/jcph.2424