Dose Reduction of Caspofungin in Intensive Care Unit Patients with Child Pugh B Will Result in Suboptimal Exposure

Autor: Martial, Lisa C., Brüggemann, Roger J. M., Schouten, Jeroen A., van Leeuwen, Henk J., van Zanten, Arthur R., de Lange, Dylan W., Muilwijk, Eline W., Verweij, Paul E., Burger, David M., Aarnoutse, Rob E., Pickkers, Peter, Dorlo, Thomas P. C., Sub Gen. Pharmacoepi and Clinical Pharm, Sub Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology
Přispěvatelé: Sub Gen. Pharmacoepi and Clinical Pharm, Sub Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
loading drug dose
Antifungal Agents
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
intensive care unit
Severity of Illness Index
Body Mass Index
law.invention
Echinocandins
chemistry.chemical_compound
Caspofungin
law
dose response
Candida albicans
polycyclic compounds
Medicine
Pharmacology (medical)
Original Research Article
caspofungin
intensive care
Aged
80 and over
clinical article
drug dose regimen
Maintenance dose
adult
article
Candidiasis
clinical trial
invasive candidiasis
Middle Aged
Farmakologi och toxikologi
Intensive care unit
aged
Intensive Care Units
female
priority journal
Female
Monte Carlo Method
medicine.drug
Adult
medicine.medical_specialty
drug exposure
Adolescent
Echinocandin
area under the curve
Metabolic Clearance Rate
030106 microbiology
NCT01533558
Microbial Sensitivity Tests
Pharmacology and Toxicology
minimum inhibitory concentration
Models
Biological
Lipopeptides
Young Adult
03 medical and health sciences
Pharmacotherapy
male
Pharmacokinetics
Internal medicine
Journal Article
Humans
human
Dosing
drug dose reduction
Intensive care medicine
Aged
Pharmacology
Dose-Response Relationship
Drug
business.industry
compartment model
bacterial infections and mycoses
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4]
chemistry
Liver function
Child Pugh score
business
plasma concentration-time curve
Zdroj: Clinical Pharmacokinetics
Clinical Pharmacokinetics, 55, 6, pp. 723-33
Clinical Pharmacokinetics, 55(6), 723. Adis International Ltd
Clinical Pharmacokinetics. Adis International Ltd
Clinical Pharmacokinetics, 55, 723-33
ISSN: 0312-5963
Popis: Contains fulltext : 172349.pdf (Publisher’s version ) (Open Access) BACKGROUND AND OBJECTIVES: Caspofungin is an echinocandin antifungal agent used as first-line therapy for the treatment of invasive candidiasis. The maintenance dose is adapted to body weight (BW) or liver function (Child-Pugh score B or C). We aimed to study the pharmacokinetics of caspofungin and assess pharmacokinetic target attainment for various dosing strategies. METHODS: Caspofungin pharmacokinetic data from 21 intensive care unit (ICU) patients was available. A population pharmacokinetic model was developed. Various dosing regimens (loading dose/maintenance dose) were simulated: licensed regimens (I) 70/50 mg (for BW 80 kg); and (II) 70/35 mg (for Child-Pugh score B); and adapted regimens (III) 100/50 mg (for Child-Pugh score B); (IV) 100/70 mg; and (V) 100/100 mg. Target attainment based on a preclinical pharmacokinetic target for Candida albicans was assessed for relevant minimal inhibitory concentrations (MICs). RESULTS: A two-compartment model best fitted the data. Clearance was 0.55 L/h and the apparent volumes of distribution in the central and peripheral compartments were 8.9 and 5.0 L, respectively. The median area under the plasma concentration-time curve from time zero to 24 h on day 14 for regimens I-V were 105, 65, 93, 130, and 186 mg.h/L, respectively. Pharmacokinetic target attainment was 100 % (MIC 0.03 microg/mL) irrespective of dosing regimen but decreased to (I) 47 %, (II) 14 %, (III) 36 %, (IV) 69 %, and (V) 94 % for MIC 0.125 microg/mL. CONCLUSION: The caspofungin maintenance dose should not be reduced in non-cirrhotic ICU patients based on the Child-Pugh score if this classification is driven by hypoalbuminemia as it results in significantly lower exposure. A higher maintenance dose of 70 mg in ICU patients results in target attainment of >90 % of the ICU patients with species with an MIC of up to 0.125 microg/mL.
Databáze: OpenAIRE
Externí odkaz: