Abstract | PURPOSE: The aim of this work was to integrate the Therapeutic Drug Monitoring (TDM) with the model-informed precision dosing (MIPD) approach, using Physiologically-based Pharmacokinetic/Pharmacodynamic (PBPK/PD) modelling and simulation, to explore the relationship between amikacin exposure and estimated glomerular filtration rate (GFR) in critically ill patients with cancer. METHODS: In the TDM study, samples from 51 critically-ill patients with cancer treated with amikacin were analysed. Patients were stratified according to renal function based on GFR status. A full-body PBPK model with 12 organs model was developed using Simcyp V. 21, including steady-state volume of distribution of 0.21 L/kg and renal clearance of 6.9 L/h in healthy adults. PK parameters evaluated were within the 2-fold error range. RESULTS: During the validation step, predicted vs observed amikacin clearance values after single infusion dose in patients with normal renal function, mild and moderate renal impairment were 7.6 vs 8.1 L/ h (7.5 mg/kg dose); 3.8 vs 4.5 L/h (1500 mg dose) and 2.2 vs 3.1 L/h (25 mg/kg dose), respectively. However, predicted vs observed amikacin clearance after a single dose infusion of 1400 mg in critically-ill patients with cancer were 1.46 vs 1.63 (P = 0.6406) L/h (severe), 2.83 vs 1.08 (P < 0.05) L/h (moderate), 4.23 vs 2.49 (P = 0.0625) L/h (mild) and 7.41 vs 3.36 (P < 0.05) L/h (normal renal function). CONCLUSION:
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Authors | João Paulo Telles, Mariana Suelotto Diegues, Karen Cristina Migotto, Olivia de Souza Borges, Rodrigo Reghini, Brenda Vianna Gavazza, Leonardo Pinto, Pedro Caruso, Ivan Leonardo França E Silva, Stephan Schmidt, Fernanda de Lima Moreira |
Journal | European journal of clinical pharmacology
(Eur J Clin Pharmacol)
Vol. 79
Issue 7
Pg. 1003-1012
(Jul 2023)
ISSN: 1432-1041 [Electronic] Germany |
PMID | 37256410
(Publication Type: Journal Article)
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Copyright | © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. |
Chemical References |
- Amikacin
- Anti-Bacterial Agents
|
Topics |
- Adult
- Humans
- Amikacin
(therapeutic use)
- Critical Illness
(therapy)
- Glomerular Filtration Rate
- Drug Monitoring
- Neoplasms
(drug therapy)
- Anti-Bacterial Agents
(therapeutic use)
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