Pharmacokinetic study of high-dose oral rifampicin in critically Ill patients with multidrug-resistant Acinetobacter baumannii infection

Purpose Although rifampicin (RIF) is used as a synergistic agent for multidrug-resistant Acinetobacter baumannii (MDR-AB) infection, the optimal pharmacokinetic (PK) indices of this medication have not been studied in the intensive care unit (ICU) settings. This study aimed to evaluate the PK of hig...

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Published in:Daru 2022-09, Vol.30 (2), p.311-322
Main Authors: Karballaei-Mirzahosseini, Hossein, Kaveh-Ahangaran, Romina, Shahrami, Bita, Rouini, Mohammad Reza, Najafi, Atabak, Ahmadi, Arezoo, Sadrai, Sima, Mojtahedzadeh, Amirmahdi, Najmeddin, Farhad, Mojtahedzadeh, Mojtaba
Format: Article
Language:English
Subjects:
Analysis
Antibiotics
Antimicrobial agents
Biomedical and Life Sciences
Biomedicine
Dosage and administration
Drug resistance in microorganisms
Health aspects
High performance liquid chromatography
Infection
Medical research
Medicinal Chemistry
Medicine, Experimental
Monte Carlo method
Multidrug resistant organisms
Pharmaceutical Sciences/Technology
Pharmacokinetics
Pharmacology/Toxicology
Research Article
Rifampin
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Summary:Purpose Although rifampicin (RIF) is used as a synergistic agent for multidrug-resistant Acinetobacter baumannii (MDR-AB) infection, the optimal pharmacokinetic (PK) indices of this medication have not been studied in the intensive care unit (ICU) settings. This study aimed to evaluate the PK of high dose oral RIF following fasting versus fed conditions in terms of achieving the therapeutic goals in critically ill patients with MDR-AB infections. Methods 29 critically ill patients were included in this study. Under fasting and non-fasting conditions, RIF was given at 1200 mg once daily through a nasogastric tube. Blood samples were obtained at seven time points: exactly before administration of the drug, and at 1, 2, 4, 8, 12, and 24 h after RIF ingestion. To quantify RIF in serum samples, high-performance liquid chromatography (HPLC) was used. The MONOLIX Software and the Monte Carlo simulations were employed to estimate the PK parameters and describe the population PK model. Results The mean area under the curve over the last 24-h (AUC 0-24 ) value and accuracy (mean ± standard deviation) in the fasting and fed states were 220.24 ± 119.15 and 290.55 ± 276.20 μg × h/mL, respectively. There was no significant difference among AUCs following fasting and non-fasting conditions (P > 0.05). The probability of reaching the therapeutic goals at the minimum inhibitory concentration (MIC) of 4 mg/L, was only 1.6%. Conclusion In critically ill patients with MDR-AB infections, neither fasting nor non-fasting administrations of high-dose oral RIF achieve the therapeutic aims. More research is needed in larger populations and with measuring the amount of protein-unbound RIF levels. Graphical abstract
ISSN:2008-2231
1560-8115
2008-2231
DOI:10.1007/s40199-022-00449-5