Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit

Abdul-Aziz, M.H. and Abd Rahman, A.N. and Mat-Nor, M.B. and Sulaiman, H. and Wallis, S.C. and Lipman, J. and Roberts, J.A. and Staatz, C.E. (2015) 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, DOI https://doi.org/10.1128/AAC.01543-15.

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Official URL: http://dx.doi.org/10.1128/AAC.01543-15


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.

Item Type: Article
Funders: International Islamic University of Malaysia Research Endowment Grant: Grant number EDW B 11-148-0626
Uncontrolled Keywords: Population; Pharmacokinetics; Doripenem; Critically ill patients; Sepsis; Malaysian intensive care unit
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 12 Oct 2017 03:16
Last Modified: 12 Oct 2017 03:16
URI: http://eprints.um.edu.my/id/eprint/17982

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