Translation of Pharmacodynamic Biomarkers of Antibiotic Efficacy in Specific Populations to Optimize Doses

Antibiotic efficacy determination in clinical trials often relies on non-inferiority designs because they afford smaller study sample sizes. These efficacy studies tend to exclude patients within specific populations or include too few patients to discern potential differences in their clinical outc...

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Autores principales:	Manjunath P. Pai, Ryan L. Crass
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	special populations pharmacokinetics antimicrobials exposure–response modeling simulation Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/46f5a6ded1c342ffb82ceb1bcc207edc
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spelling	oai:doaj.org-article:46f5a6ded1c342ffb82ceb1bcc207edc2021-11-25T16:23:56ZTranslation of Pharmacodynamic Biomarkers of Antibiotic Efficacy in Specific Populations to Optimize Doses10.3390/antibiotics101113682079-6382https://doaj.org/article/46f5a6ded1c342ffb82ceb1bcc207edc2021-11-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1368https://doaj.org/toc/2079-6382Antibiotic efficacy determination in clinical trials often relies on non-inferiority designs because they afford smaller study sample sizes. These efficacy studies tend to exclude patients within specific populations or include too few patients to discern potential differences in their clinical outcomes. As a result, dosing guidance in patients with abnormal liver and kidney function, age across the lifespan, and other specific populations relies on drug exposure-matching. The underlying assumption for exposure-matching is that the disease course and the response to the antibiotic are similar in patients with and without the specific condition. While this may not be the case, clinical efficacy studies are underpowered to ensure this is true. The current paper provides an integrative review of the current approach to dose selection in specific populations. We review existing clinical trial endpoints that could be measured on a more continuous rather than a discrete scale to better inform exposure–response relationships. The inclusion of newer systemic biomarkers of efficacy can help overcome the current limitations. We use a modeling and simulation exercise to illustrate how an efficacy biomarker can inform dose selection better. Studies that inform response-matching rather than exposure-matching only are needed to improve dose selection in specific populations.Manjunath P. PaiRyan L. CrassMDPI AGarticlespecial populationspharmacokineticsantimicrobialsexposure–responsemodelingsimulationTherapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1368, p 1368 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	special populations pharmacokinetics antimicrobials exposure–response modeling simulation Therapeutics. Pharmacology RM1-950
spellingShingle	special populations pharmacokinetics antimicrobials exposure–response modeling simulation Therapeutics. Pharmacology RM1-950 Manjunath P. Pai Ryan L. Crass Translation of Pharmacodynamic Biomarkers of Antibiotic Efficacy in Specific Populations to Optimize Doses
description	Antibiotic efficacy determination in clinical trials often relies on non-inferiority designs because they afford smaller study sample sizes. These efficacy studies tend to exclude patients within specific populations or include too few patients to discern potential differences in their clinical outcomes. As a result, dosing guidance in patients with abnormal liver and kidney function, age across the lifespan, and other specific populations relies on drug exposure-matching. The underlying assumption for exposure-matching is that the disease course and the response to the antibiotic are similar in patients with and without the specific condition. While this may not be the case, clinical efficacy studies are underpowered to ensure this is true. The current paper provides an integrative review of the current approach to dose selection in specific populations. We review existing clinical trial endpoints that could be measured on a more continuous rather than a discrete scale to better inform exposure–response relationships. The inclusion of newer systemic biomarkers of efficacy can help overcome the current limitations. We use a modeling and simulation exercise to illustrate how an efficacy biomarker can inform dose selection better. Studies that inform response-matching rather than exposure-matching only are needed to improve dose selection in specific populations.
format	article
author	Manjunath P. Pai Ryan L. Crass
author_facet	Manjunath P. Pai Ryan L. Crass
author_sort	Manjunath P. Pai
title	Translation of Pharmacodynamic Biomarkers of Antibiotic Efficacy in Specific Populations to Optimize Doses
title_short	Translation of Pharmacodynamic Biomarkers of Antibiotic Efficacy in Specific Populations to Optimize Doses
title_full	Translation of Pharmacodynamic Biomarkers of Antibiotic Efficacy in Specific Populations to Optimize Doses
title_fullStr	Translation of Pharmacodynamic Biomarkers of Antibiotic Efficacy in Specific Populations to Optimize Doses
title_full_unstemmed	Translation of Pharmacodynamic Biomarkers of Antibiotic Efficacy in Specific Populations to Optimize Doses
title_sort	translation of pharmacodynamic biomarkers of antibiotic efficacy in specific populations to optimize doses
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/46f5a6ded1c342ffb82ceb1bcc207edc
work_keys_str_mv	AT manjunathppai translationofpharmacodynamicbiomarkersofantibioticefficacyinspecificpopulationstooptimizedoses AT ryanlcrass translationofpharmacodynamicbiomarkersofantibioticefficacyinspecificpopulationstooptimizedoses
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Translation of Pharmacodynamic Biomarkers of Antibiotic Efficacy in Specific Populations to Optimize Doses

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