2023
DOI: 10.1007/s40262-023-01217-7
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Predictions of Bedaquiline and Pretomanid Target Attainment in Lung Lesions of Tuberculosis Patients using Translational Minimal Physiologically Based Pharmacokinetic Modeling

Abstract: Background Site-of-action concentrations for bedaquiline and pretomanid from tuberculosis patients are unavailable. The objective of this work was to predict bedaquiline and pretomanid site-of-action exposures using a translational minimal physiologically based pharmacokinetic (mPBPK) approach to understand the probability of target attainment (PTA). Methods A general translational mPBPK framework for the prediction of lung and lung lesion exposure was developed and val… Show more

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Cited by 10 publications
(22 citation statements)
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References 37 publications
(53 reference statements)
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“…33 Based on our translational mPBPK model, plasma, lungs and lesion M2-bedaquiline exposure ratios were predicted to be 0.18, 1.11 and 1.02, respectively. 14 These results provide an overview of the relative role of M2 as compared to bedaquiline on Mtb clearance.…”
Section: Simulations Of Anti-mtb Activity Following Bpal At Approved ...mentioning
confidence: 94%
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“…33 Based on our translational mPBPK model, plasma, lungs and lesion M2-bedaquiline exposure ratios were predicted to be 0.18, 1.11 and 1.02, respectively. 14 These results provide an overview of the relative role of M2 as compared to bedaquiline on Mtb clearance.…”
Section: Simulations Of Anti-mtb Activity Following Bpal At Approved ...mentioning
confidence: 94%
“…12,[22][23][24] PK models and parameter estimates for bedaquiline and pretomanid from our prior work were used to simulate plasma and site of action, lungs and lesions, and concentration-time profiles. 14 A PK model for linezolid was reproduced from the literature to simulate plasma, lungs and lesion concentration-time profiles. 25 Body weights were sampled for the virtual patients from observed TB patients' body weight distribution from the data.…”
Section: Mechanistic Pk-pd Modelsmentioning
confidence: 99%
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