Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN)

Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR) Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-...

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Veröffentlicht in:Antimicrobial agents and chemotherapy 2021-02, Vol.65 (3)
Hauptverfasser: Lodise, Thomas P, Van Wart, Scott, Sund, Zoe M, Bressler, Adam M, Khan, Akram, Makley, Amy T, Hamad, Yasir, Salata, Robert A, Silveira, Fernanda P, Sims, Matthew D, Kabchi, Badih A, Saad, Mohamed A, Brown, Carrie, Oler, Jr, Randolph E, Fowler, Jr, Vance, Wunderink, Richard G
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container_issue 3
container_start_page
container_title Antimicrobial agents and chemotherapy
container_volume 65
creator Lodise, Thomas P
Van Wart, Scott
Sund, Zoe M
Bressler, Adam M
Khan, Akram
Makley, Amy T
Hamad, Yasir
Salata, Robert A
Silveira, Fernanda P
Sims, Matthew D
Kabchi, Badih A
Saad, Mohamed A
Brown, Carrie
Oler, Jr, Randolph E
Fowler, Jr, Vance
Wunderink, Richard G
description Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR) Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of i.v. minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200-mg i.v. dose of minocycline. Plasma PK samples were collected predose and 1, 4, 12, 24, 36, and 48 h after initiation of minocycline. Total and unbound minocycline concentrations were determined at each time point. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (free area under the curve above the MIC [ AUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (f ) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with f ). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation.
doi_str_mv 10.1128/AAC.01809-20
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A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (f ) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with f ). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with infections with MIC values of &gt;1 mg/liter. 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source MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central
subjects Acinetobacter baumannii
Adult
Animals
Anti-Bacterial Agents - therapeutic use
Clinical Therapeutics
Critical Illness
Humans
Microbial Sensitivity Tests
Minocycline
title Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN)
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