Population pharmacokinetics of doripenem in critically ill patients with sepsis in a Malaysian intensive care unit

Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with...

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Main Authors:	Abdul Aziz, Mohd. Hafiz, Abd. Rahman, Nurul Azrin, Mat Nor, Mohd Basri, Sulaiman, Helmi, Wallis, Steven C., Lipman, Jeffrey, Roberts, Jason A., Staatz, Christine E.
Format:	Article
Language:	English English
Published:	American Society for Microbiolog 2016
Subjects:	QR Microbiology RM300 Drugs and their action RS Pharmacy and materia medica
Online Access:	http://irep.iium.edu.my/46664/ http://irep.iium.edu.my/46664/ http://irep.iium.edu.my/46664/ http://irep.iium.edu.my/46664/4/46664_Population_Pharmacokinetics_WOS_Scopus.pdf http://irep.iium.edu.my/46664/6/Item_ID_46664.pdf

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spelling	iium-466642017-04-06T08:11:48Z http://irep.iium.edu.my/46664/ Population pharmacokinetics of doripenem in critically ill patients with sepsis in a Malaysian intensive care unit Abdul Aziz, Mohd. Hafiz Abd. Rahman, Nurul Azrin Mat Nor, Mohd Basri Sulaiman, Helmi Wallis, Steven C. Lipman, Jeffrey Roberts, Jason A. Staatz, Christine E. QR Microbiology RM300 Drugs and their action RS Pharmacy and materia medica Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CLCR), such that a 30-ml/min increase in the estimated CLCR would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every8hasa4-hinfusion is optimal for patients with a CLCR of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CLCR of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved American Society for Microbiolog 2016-01-01 Article PeerReviewed application/pdf en http://irep.iium.edu.my/46664/4/46664_Population_Pharmacokinetics_WOS_Scopus.pdf application/pdf en http://irep.iium.edu.my/46664/6/Item_ID_46664.pdf Abdul Aziz, Mohd. Hafiz and Abd. Rahman, Nurul Azrin and Mat Nor, Mohd Basri and Sulaiman, Helmi and Wallis, Steven C. and Lipman, Jeffrey and Roberts, Jason A. and Staatz, Christine E. (2016) Population pharmacokinetics of doripenem in critically ill patients with sepsis in a Malaysian intensive care unit. Antimicrobial agents and chemotherapy, 60 (1). pp. 206-214. ISSN 0066-4804 E-ISSN 1098-6596 http://aac.asm.org/content/early/2015/10/13/AAC.01543-15.abstract 10.1128/AAC.01543-15
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English
topic	QR Microbiology RM300 Drugs and their action RS Pharmacy and materia medica
spellingShingle	QR Microbiology RM300 Drugs and their action RS Pharmacy and materia medica Abdul Aziz, Mohd. Hafiz Abd. Rahman, Nurul Azrin Mat Nor, Mohd Basri Sulaiman, Helmi Wallis, Steven C. Lipman, Jeffrey Roberts, Jason A. Staatz, Christine E. Population pharmacokinetics of doripenem in critically ill patients with sepsis in a Malaysian intensive care unit
description	Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CLCR), such that a 30-ml/min increase in the estimated CLCR would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every8hasa4-hinfusion is optimal for patients with a CLCR of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CLCR of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved
format	Article
author	Abdul Aziz, Mohd. Hafiz Abd. Rahman, Nurul Azrin Mat Nor, Mohd Basri Sulaiman, Helmi Wallis, Steven C. Lipman, Jeffrey Roberts, Jason A. Staatz, Christine E.
author_facet	Abdul Aziz, Mohd. Hafiz Abd. Rahman, Nurul Azrin Mat Nor, Mohd Basri Sulaiman, Helmi Wallis, Steven C. Lipman, Jeffrey Roberts, Jason A. Staatz, Christine E.
author_sort	Abdul Aziz, Mohd. Hafiz
title	Population pharmacokinetics of doripenem in critically ill patients with sepsis in a Malaysian intensive care unit
title_short	Population pharmacokinetics of doripenem in critically ill patients with sepsis in a Malaysian intensive care unit
title_full	Population pharmacokinetics of doripenem in critically ill patients with sepsis in a Malaysian intensive care unit
title_fullStr	Population pharmacokinetics of doripenem in critically ill patients with sepsis in a Malaysian intensive care unit
title_full_unstemmed	Population pharmacokinetics of doripenem in critically ill patients with sepsis in a Malaysian intensive care unit
title_sort	population pharmacokinetics of doripenem in critically ill patients with sepsis in a malaysian intensive care unit
publisher	American Society for Microbiolog
publishDate	2016
url	http://irep.iium.edu.my/46664/ http://irep.iium.edu.my/46664/ http://irep.iium.edu.my/46664/ http://irep.iium.edu.my/46664/4/46664_Population_Pharmacokinetics_WOS_Scopus.pdf http://irep.iium.edu.my/46664/6/Item_ID_46664.pdf
first_indexed	2023-09-18T21:06:26Z
last_indexed	2023-09-18T21:06:26Z
_version_	1777410964176502784

Population pharmacokinetics of doripenem in critically ill patients with sepsis in a Malaysian intensive care unit

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