Document Detail


Posaconazole plasma concentrations in critically ill patients.
MedLine Citation:
PMID:  21654350     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Posaconazole is an azole antifungal agent with a broad spectrum of activity and a manageable side-effect profile. Although the pharmacokinetics of posaconazole have been described in healthy volunteers who received the drug by means of a nasogastric tube or with nutritional supplements, the pharmacokinetics of posaconazole have not been reported in critically ill patients.
METHODS: Twenty-seven patients in the general intensive care unit managed according to standard protocols were randomly allocated to dose regimens of either 400 mg twice daily or 200 mg 4 times daily. Plasma samples were collected for pharmacokinetic analysis after the first dose and at steady-state. Posaconazole plasma concentrations were compared with suggested effect targets for prophylaxis and treatment.
RESULTS: Mean Cmin steady-state plasma concentrations of posaconazole were low for both regimens (306 and 137 ng/mL for 400 mg twice daily and 200 mg 4 times daily regimens, respectively), as was total exposure to posaconazole in each group [area under the concentration-time curve (AUC0-t) for first dose: 761 and 299 μg·h/L]. Only 17% of patients achieved steady-state Cmin posaconazole plasma concentrations above the suggested target for prophylaxis, and only one patient had a Cmin posaconazole concentration that exceeded the suggested target for treatment effect. Systemic exposure to posaconazole seemed to be subtherapeutic in most patients in this cohort. Poor absorption of posaconazole due to drug interactions may explain the low systemic exposure; however, further investigation is necessary.
CONCLUSIONS: These data suggest that there is a need for an intraveneous formulation of the drug if it is to be used effectively in critically ill patients, and therapeutic drug monitoring is an essential tool in this setting to identify patients with low systemic exposure to prevent therapeutic failure.
Authors:
John Ray; Lewis Campbell; Sam Rudham; Quoc Nguyen; Deborah Marriott
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  33     ISSN:  1536-3694     ISO Abbreviation:  Ther Drug Monit     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-18     Completed Date:  2012-01-05     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  United States    
Other Details:
Languages:  eng     Pagination:  387-92     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antifungal Agents / administration & dosage*,  blood*,  pharmacokinetics
Area Under Curve
Critical Illness*
Dose-Response Relationship, Drug
Drug Monitoring / methods
Female
Humans
Intensive Care Units
Intubation, Gastrointestinal
Male
Middle Aged
Triazoles / administration & dosage*,  blood*,  pharmacokinetics
Chemical
Reg. No./Substance:
0/Antifungal Agents; 0/Triazoles; 6TK1G07BHZ/posaconazole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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