Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration
Here we describe the pharmacokinetics of piperacillin administered by continuous infusion (CI) versus intermittent bolus (IB) dosing in critically ill patients receiving continuous venovenous haemofiltration (CVVH) and compare the frequency of pharmacodynamic/pharmacokin...
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Elsevier
2015
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| Online Access: | http://irep.iium.edu.my/43883/ http://irep.iium.edu.my/43883/1/Pharmacokinetics_of_piperacillin_in_critically_ill_patients_receiving_continuous_venovenous_haemofiltration_A_randomised_controlled_trial_of_continuous_infusion_versus_intermi.pdf http://irep.iium.edu.my/43883/4/43883_Pharmacokinetics%20of%20piperacillin%20in%20critically%20ill%20patients%20receiving%20continuous%20venovenous%20haemofiltration_SCOPUS.pdf |
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| author | Jamal, Janattul-Ain Roberts, Darren M. Udy, Andrew A Mat Nor, Mohd Basri Mohamad Nor, Fariz Safhan Wallis, Steven C Lipman, Jeffrey Roberts, Jason A. |
| author_facet | Jamal, Janattul-Ain Roberts, Darren M. Udy, Andrew A Mat Nor, Mohd Basri Mohamad Nor, Fariz Safhan Wallis, Steven C Lipman, Jeffrey Roberts, Jason A. |
| author_sort | Jamal, Janattul-Ain |
| building | IIUM Repository |
| collection | Online Access |
| description | Here we describe the pharmacokinetics of piperacillin administered by continuous infusion (CI) versus intermittent bolus (IB) dosing in critically ill patients receiving continuous venovenous haemofiltration (CVVH) and compare the frequency of pharmacodynamic/pharmacokinetic (PK/PD) target attainment with each dosing strategy. This was a prospective pharmacokinetic trial in 16 critically ill patients with severe sepsis or septic shock undergoing CVVH and randomised to receive either CI or IB administration of a standard daily dose of piperacillin/tazobactam (11.25 g/day on Day 1 followed by 9 g/day). Serial blood samples were measured on two occasions. Piperacillin pharmacokinetics were calculated using a non-compartmental approach. Blood concentrations were compared with established PK/PD targets. On occasion 1 (Days 1–3 of therapy), IB administration resulted in significantly higher piperacillin peak concentrations (169 vs. 89 mg/L; P = 0.002), whereas significantly higher steady-state concentrations were observed in CI patients (83 vs. 57 mg/L; P = 0.04). Total clearance and clearance not mediated by CVVH were significantly higher with CI administration [median (interquartile range), 1.0 (0.7–1.1) and 0.8 (0.6–1.0) mL/kg/min; P = 0.001 and 0.001, respectively]. The estimated unbound piperacillin conncentrations were four times above the target susceptibility breakpoint (16 mg/L) for the entire dosing interval (100%fT>4xMIC) in 87.5% of patients receiving CI administration (sampling occasion 1), compared with 62.5% of IB patients achieving the desired target (50%fT>4xMIC). Compared with IB dosing, and despite similar CVVH settings, CI administration of piperacillin results in a pharmacokinetic profile that may optimise outcomes for less susceptible pathogens. |
| first_indexed | 2025-11-14T16:06:44Z |
| format | Article |
| id | iium-43883 |
| institution | International Islamic University Malaysia |
| institution_category | Local University |
| language | English English |
| last_indexed | 2025-11-14T16:06:44Z |
| publishDate | 2015 |
| publisher | Elsevier |
| recordtype | eprints |
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| spelling | iium-438832017-11-15T03:52:51Z http://irep.iium.edu.my/43883/ Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration Jamal, Janattul-Ain Roberts, Darren M. Udy, Andrew A Mat Nor, Mohd Basri Mohamad Nor, Fariz Safhan Wallis, Steven C Lipman, Jeffrey Roberts, Jason A. RS Pharmacy and materia medica Here we describe the pharmacokinetics of piperacillin administered by continuous infusion (CI) versus intermittent bolus (IB) dosing in critically ill patients receiving continuous venovenous haemofiltration (CVVH) and compare the frequency of pharmacodynamic/pharmacokinetic (PK/PD) target attainment with each dosing strategy. This was a prospective pharmacokinetic trial in 16 critically ill patients with severe sepsis or septic shock undergoing CVVH and randomised to receive either CI or IB administration of a standard daily dose of piperacillin/tazobactam (11.25 g/day on Day 1 followed by 9 g/day). Serial blood samples were measured on two occasions. Piperacillin pharmacokinetics were calculated using a non-compartmental approach. Blood concentrations were compared with established PK/PD targets. On occasion 1 (Days 1–3 of therapy), IB administration resulted in significantly higher piperacillin peak concentrations (169 vs. 89 mg/L; P = 0.002), whereas significantly higher steady-state concentrations were observed in CI patients (83 vs. 57 mg/L; P = 0.04). Total clearance and clearance not mediated by CVVH were significantly higher with CI administration [median (interquartile range), 1.0 (0.7–1.1) and 0.8 (0.6–1.0) mL/kg/min; P = 0.001 and 0.001, respectively]. The estimated unbound piperacillin conncentrations were four times above the target susceptibility breakpoint (16 mg/L) for the entire dosing interval (100%fT>4xMIC) in 87.5% of patients receiving CI administration (sampling occasion 1), compared with 62.5% of IB patients achieving the desired target (50%fT>4xMIC). Compared with IB dosing, and despite similar CVVH settings, CI administration of piperacillin results in a pharmacokinetic profile that may optimise outcomes for less susceptible pathogens. Elsevier 2015-07-01 Article PeerReviewed application/pdf en http://irep.iium.edu.my/43883/1/Pharmacokinetics_of_piperacillin_in_critically_ill_patients_receiving_continuous_venovenous_haemofiltration_A_randomised_controlled_trial_of_continuous_infusion_versus_intermi.pdf application/pdf en http://irep.iium.edu.my/43883/4/43883_Pharmacokinetics%20of%20piperacillin%20in%20critically%20ill%20patients%20receiving%20continuous%20venovenous%20haemofiltration_SCOPUS.pdf Jamal, Janattul-Ain and Roberts, Darren M. and Udy, Andrew A and Mat Nor, Mohd Basri and Mohamad Nor, Fariz Safhan and Wallis, Steven C and Lipman, Jeffrey and Roberts, Jason A. (2015) Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration. International Journal of Antimicrobial Agents, 46 (1). pp. 39-44. ISSN 0924-8579 http://www.sciencedirect.com/science/article/pii/S0924857915001089 10.1016/j.ijantimicag.2015.02.014 |
| spellingShingle | RS Pharmacy and materia medica Jamal, Janattul-Ain Roberts, Darren M. Udy, Andrew A Mat Nor, Mohd Basri Mohamad Nor, Fariz Safhan Wallis, Steven C Lipman, Jeffrey Roberts, Jason A. Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration |
| title | Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration |
| title_full | Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration |
| title_fullStr | Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration |
| title_full_unstemmed | Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration |
| title_short | Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration |
| title_sort | pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration |
| topic | RS Pharmacy and materia medica |
| url | http://irep.iium.edu.my/43883/ http://irep.iium.edu.my/43883/ http://irep.iium.edu.my/43883/ http://irep.iium.edu.my/43883/1/Pharmacokinetics_of_piperacillin_in_critically_ill_patients_receiving_continuous_venovenous_haemofiltration_A_randomised_controlled_trial_of_continuous_infusion_versus_intermi.pdf http://irep.iium.edu.my/43883/4/43883_Pharmacokinetics%20of%20piperacillin%20in%20critically%20ill%20patients%20receiving%20continuous%20venovenous%20haemofiltration_SCOPUS.pdf |