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Population Pharmaco...
Population Pharmacokinetics of Delamanid and its Main Metabolite DM-6705 in Drug-Resistant Tuberculosis Patients Receiving Delamanid Alone or Coadministered with Bedaquiline
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- Tanneau, Lénaïg (författare)
- Uppsala universitet,Institutionen för farmaci,Pharmacometrics
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- Karlsson, Mats (författare)
- Uppsala universitet,Institutionen för farmaci,Pharmacometrics
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- Diacon, Andreas H (författare)
- TASK Applied Science, Cape Town, South Africa
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- Shenje, Justin (författare)
- SATVI, University of Cape Town, South Africa
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- De los rios, Jorge (författare)
- Barranco Clinical Research Site, Asociacion Civil Impacta Salud y Educacion, Lima, Peru
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- Wiesner, Lubbe (författare)
- Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
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- Upton, Caryn M (författare)
- TASK Applied Science, Cape Town, South Africa
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- Dooley, Kelly E (författare)
- Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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- Maartens, Gary (författare)
- Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
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- Svensson, Elin, 1985- (författare)
- Uppsala universitet,Institutionen för farmaci,Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands,pharmacometrics
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(creator_code:org_t)
- 2022-06-07
- 2022
- Engelska.
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Ingår i: Clinical Pharmacokinetics. - : Springer. - 0312-5963 .- 1179-1926.
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Delamanid is a nitroimidazole, a novel class of drug for treating tuberculosis. Delamanid is primarily metabolized by albumin into the metabolite DM-6705. The aims of this analysis were to develop a population pharmacokinetic (PK) model to characterize the concentration-time course of delamanid and DM-6705 in adults with drug-resistant tuberculosis and to explore a potential drug-drug interaction with bedaquiline when co-administered. Methods: Delamanid and DM-6705 concentrations after oral administration, from 52 participants (of whom 26 took bedaquiline concurrently and 20 were HIV-1 positive) enrolled in the DELIBERATE trial were analyzed using nonlinear mixed-effects modeling.Results: Delamanid PK was described by a one-compartment disposition model with transit compartment absorption (mean absorption time of 1.45 h (95% confidence interval 0.501–2.20)) and linear elimination. The PK of DM-6705 metabolite, was described by a one-compartment disposition model with delamanid clearance as input and linear elimination. Predicted terminal half-life values for delamanid and DM-6705 were 15.1 hours and 7.8 days, respectively. The impact of plasma albumin concentrations on delamanid metabolism was not significant. Bedaquiline co-administration did not affect delamanid PK. Other than allometric scaling with body weight, no patients’ demographics were significant (including HIV). Conclusions: This is the first published joint PK model of delamanid and its DM-6705 metabolite. As such, it can be utilized in future exposure-response or exposure-safety analyses. Importantly, albumin concentrations, bedaquiline co-administration, and HIV co-infection (dolutegravir co-administration) did not have an effect on delamanid and DM-6705 PK.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- non-linear mixed effects model
- pharmacokinetics
- delamanid
- metabolite
- tuberculosis
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- ref (ämneskategori)
- art (ämneskategori)
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Tanneau, Lénaïg
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Karlsson, Mats
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Diacon, Andreas ...
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Shenje, Justin
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De los rios, Jor ...
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Wiesner, Lubbe
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visa fler...
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Upton, Caryn M
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Dooley, Kelly E
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Maartens, Gary
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Svensson, Elin, ...
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