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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).

Publication ,  Journal Article
Lodise, TP; Van Wart, S; Sund, ZM; Bressler, AM; Khan, A; Makley, AT; Hamad, Y; Salata, RA; Silveira, FP; Sims, MD; Kabchi, BA; Saad, MA ...
Published in: Antimicrobial agents and chemotherapy
February 2021

Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR) Acinetobacter baumannii 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 [fAUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of A. baumannii were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (fub) 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 fub). 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 A. baumannii infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation.

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Published In

Antimicrobial agents and chemotherapy

DOI

EISSN

1098-6596

ISSN

0066-4804

Publication Date

February 2021

Volume

65

Issue

3

Start / End Page

e01809 / e01820

Related Subject Headings

  • Minocycline
  • Microbiology
  • Microbial Sensitivity Tests
  • Humans
  • Critical Illness
  • Anti-Bacterial Agents
  • Animals
  • Adult
  • Acinetobacter baumannii
  • 3214 Pharmacology and pharmaceutical sciences
 

Citation

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Lodise, T. P., Van Wart, S., Sund, Z. M., Bressler, A. M., Khan, A., Makley, A. T., … Wunderink, R. G. (2021). 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). Antimicrobial Agents and Chemotherapy, 65(3), e01809–e01820. https://doi.org/10.1128/aac.01809-20
Lodise, Thomas P., Scott Van Wart, Zoe M. Sund, Adam M. Bressler, Akram Khan, Amy T. Makley, Yasir Hamad, et al. “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).Antimicrobial Agents and Chemotherapy 65, no. 3 (February 2021): e01809–20. https://doi.org/10.1128/aac.01809-20.
Lodise TP, Van Wart S, Sund ZM, Bressler AM, Khan A, Makley AT, et al. 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). Antimicrobial agents and chemotherapy. 2021 Feb;65(3):e01809–20.
Lodise, Thomas P., et al. “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).Antimicrobial Agents and Chemotherapy, vol. 65, no. 3, Feb. 2021, pp. e01809–20. Epmc, doi:10.1128/aac.01809-20.
Lodise TP, Van Wart S, Sund ZM, Bressler AM, Khan A, Makley AT, Hamad Y, Salata RA, Silveira FP, Sims MD, Kabchi BA, Saad MA, Brown C, Oler RE, Fowler V, Wunderink RG. 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). Antimicrobial agents and chemotherapy. 2021 Feb;65(3):e01809–e01820.

Published In

Antimicrobial agents and chemotherapy

DOI

EISSN

1098-6596

ISSN

0066-4804

Publication Date

February 2021

Volume

65

Issue

3

Start / End Page

e01809 / e01820

Related Subject Headings

  • Minocycline
  • Microbiology
  • Microbial Sensitivity Tests
  • Humans
  • Critical Illness
  • Anti-Bacterial Agents
  • Animals
  • Adult
  • Acinetobacter baumannii
  • 3214 Pharmacology and pharmaceutical sciences