Herbert Spapen, Johan van Laethem, Maya Hites, An Verdoodt, Marc Diltoer and Patrick M. Honoré
the 1970s because of significant renal and neurological toxicity. [ 4 ] At present, COL is increasingly put forward as salvage or first-line treatment for severe MDR-GNB infections, particularly in the ICU. [ 5 ] COL is administered intravenously as the inactive prodrug colistimethate sodium (CMS) that is hydrolyzed to COL. From a pharmacodynamic/pharmacokinetic (PK/PD) viewpoint, COL possesses rapid concentration-dependent bacterial killing against susceptible strains, but the ratio of the area under the concentration time curve of the unbound fraction to the
Patrick M. Honore, David De Bels, Luc Kugener, Sebastien Redant, Rachid Attou, Andrea Gallerani and Herbert D. Spapen
To the editor
Pharmacokinetic and dose-response data suggest a vitamin C (vit C) dose largely exceeding 3 g daily in critically ill patients. We recently proposed higher vit C dosing in cardiac arrest patients who require continuous renal replacement therapy (CRRT).[ 1 ] In a reaction, Spoelstra-de Man et al . rebutted that increasing the vit C dose above 2 g/day during continuous veno-venous hemofiltration (CVVH) was unnecessary when normal plasma vit C concentrations are targeted. They based their standpoint on calculating less vit C removal during CVVH
Patrick M. Honore, Rita Jacobs, Olivier Joannes-Boyau, Willem Boer, Elisabeth De Waele, Viola Van Gorp and Herbert D. Spapen
1. Spapen HD, Jacobs R, Van Gorp V, Troubleyn J, Honoré PM. Renal and neurological side effects of colistin in critically ill patients. Ann Intensive Care 2011;1:14.
2. Bergen PJ, Li J, Rayner CR, Nation RL. Colistin methanesulfonate is an inactive prodrug of colistin against Pseudomonas aeruginosa.Antimicrob Agents Chemother 2006;50:1953-8.
3. Couet W, Grégoire N, Marchand S, Mimoz O. Colistin pharmacokinetics: The fog is lifting. Clin Microbiol Infect 2012;18:30-9.
4. Yahav D
Ayman Geddawy, Yasmine F. Ibrahim, Nabil M. Elbahie and Mohammad A. Ibrahim
approved in combination with PegIFN-alpha and ribavirin for the treatment of chronic HCV genotype 1 infection in 2011.  However, these drugs have been reported to have several drug-drug interactions, and are largely replaced with newer DAA including Simeprevir, Paritaprevir, Daclatasvir, Ledipasvir, Ombitasvir, Sofosbuvir and Dasabuvir. Table 3 summarizes the pharmacokinetics of all approved DAA with special reference to the sites of drug-drug interaction. Clinical pharmacology of the newer DAA will be discussed in the next section.
Patrick M. Honore, Rita Jacobs, Olivier Joannes-Boyau, Elisabeth De Waele and Herbert D. Spapen
. Endocrinology in Intensive Care Medicine: New Insights and Therapeutic Consequences. Verh K Acad Geneeskd Belg 2002;64:167-87.
16. Amer MR, Akhras NS, Mahmood WA, Al-Jazairi AS. Antimicrobial Stewardship Program Implementation in a medical intensive care unit in a tertiary hospital in Saudi Arabia. Ann Saudi Med 2013;33:547-54.
17. Honore PM, Jacobs R, Spapen HD. Impact of altered antimicrobial pharmacokinetics on antimicrobial dosing during extracorporeal membrane oxygenation. Annu Update Intensive Care Emerg Med 2014;34 [In Press
favorable data on the DOACs but they are not licensed for this indication yet. However, it should be remembered that rivaroxaban is contraindicated in patients with advanced cirrhosis (Child class B and C), after a pharmacokinetic study showed increased rivaroxaban concentrations in patients with moderate hepatic impairment;[ 32 , 33 ] while apixaban has the highest percentage of hepatic metabolism (up to 73%) and therefore should be used with caution in patients with mild or moderate liver impairment (Child class A and B), it is not recommended in patients with severe
e3182816a75 Honore PM Jacobs R Joannes-Boyau O De Regt J De Waele E van Gorp V Newly designed CRRT membranes for sepsis and SIRS--a pragmatic approach for bedside intensivists summarizing the more recent advances: a systematic structured review ASAIO J 2013 59 99 106
16 Honore PM, Jacobs R, De Waele E, Spapen HD. Applying pharmacokinetic/pharmacodynamic principles for optimizing antimicrobial therapy during continuous renal replacement therapy. Anaesthesiol Intensive Ther 2017; 49: 412-8. 10.5603/AIT.a2017.0071 Honore PM Jacobs R De Waele E Spapen HD. Applying
the definition, mechanism, clinical impacts, detection, and intervention of aspirin resistance.
Definition of Aspirin Resistance
The concept of aspirin therapy response variability is mainly based on specific pathophysiological mechanisms, pharmacokinetics, and/ or pharmacodynamics by which aspirin works. aspirin resistance may be simply one of potential causes leading to interindividual variability in the response to aspirin. [ 1 ] In 2009, the Working Group on Thrombosis of the European Society of Cardiology released a position paper on interindividual