Dose recommendations for intravenous colistin in pediatric patients from a prospective, multicenter, population pharmacokinetic study

Objectives: The aim of this study was to describe the population pharmacokinetics of intravenous colistin use in children and to propose optimal dosage regimens. Methods: A prospective, multicenter, population pharmacokinetic (PPK) study was conducted. Phoenix 64 version 8.3 was used for the PPK ana...

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Main Authors: Noppadol Wacharachaisurapol, Warumphon Sukkummee, Orawan Anunsittichai, Panida Srisan, Siriporn Sangkhamal, Prawat Chantharit, Warunee Punpanich Vandepitte, Thitima Wattanavijitkul, Thanyawee Puthanakit
Format: Article
Language:English
Published: Elsevier 2021-08-01
Series:International Journal of Infectious Diseases
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1201971221005397
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author Noppadol Wacharachaisurapol
Warumphon Sukkummee
Orawan Anunsittichai
Panida Srisan
Siriporn Sangkhamal
Prawat Chantharit
Warunee Punpanich Vandepitte
Thitima Wattanavijitkul
Thanyawee Puthanakit
author_facet Noppadol Wacharachaisurapol
Warumphon Sukkummee
Orawan Anunsittichai
Panida Srisan
Siriporn Sangkhamal
Prawat Chantharit
Warunee Punpanich Vandepitte
Thitima Wattanavijitkul
Thanyawee Puthanakit
author_sort Noppadol Wacharachaisurapol
collection DOAJ
description Objectives: The aim of this study was to describe the population pharmacokinetics of intravenous colistin use in children and to propose optimal dosage regimens. Methods: A prospective, multicenter, population pharmacokinetic (PPK) study was conducted. Phoenix 64 version 8.3 was used for the PPK analysis. Simulations were performed to estimate the probability of target attainment for patients achieving target plasma colistin average steady-state concentrations (Css,avg). Results: A total of 334 plasma colistin concentrations were obtained from 79 pediatric patients with a median age (interquartile range) of 2.6 years (0.8−6.8 years); 73 (92.4%) were admitted to intensive care units. Colistin pharmacokinetics were adequately described by a one-compartment model with first-order elimination along with serum creatinine (SCr) as a significant covariate in colistin clearance. The simulation demonstrated that the recommended dose of 5 mg of colistin base activity (CBA)/kg/day resulted in 18.2−63.0% probability of achieving a target Css,avg of 2 mg/l. With a lower targeted Css,avg of 1 mg/l, colistin dosing with 7.5 mg and 5 mg of CBA/kg/day were adequate for children with SCr levels of 0.1−0.3 mg/dl and >0.3 mg/dl, respectively. Conclusions: SCr is a significant covariate in colistin clearance in children. Colistin dosing should be selected according to the patient's SCr level and the desired target Css,avg.
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spelling doaj.art-1db2e00ec03b4a60a3c2d765722a6bd02022-12-21T22:02:59ZengElsevierInternational Journal of Infectious Diseases1201-97122021-08-01109230237Dose recommendations for intravenous colistin in pediatric patients from a prospective, multicenter, population pharmacokinetic studyNoppadol Wacharachaisurapol0Warumphon Sukkummee1Orawan Anunsittichai2Panida Srisan3Siriporn Sangkhamal4Prawat Chantharit5Warunee Punpanich Vandepitte6Thitima Wattanavijitkul7Thanyawee Puthanakit8Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandClinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandCentre of Excellence for Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandDivision of Pulmonary and Critical Care, Department of Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, ThailandPediatric Intensive Care Unit, Queen Sirikit National Institute of Child Health, Bangkok, ThailandDivision of Infectious Diseases, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandQueen Sirikit National Institute of Child Health, Bangkok, Thailand; College of Medicine, Rangsit University, Bangkok, ThailandDepartment of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, ThailandCentre of Excellence for Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Corresponding author: Thanyawee Puthanakit, Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, 1873 Rama IV Road, Pathumwan, Bangkok, Thailand, 10330. Tel: +6622564930.Objectives: The aim of this study was to describe the population pharmacokinetics of intravenous colistin use in children and to propose optimal dosage regimens. Methods: A prospective, multicenter, population pharmacokinetic (PPK) study was conducted. Phoenix 64 version 8.3 was used for the PPK analysis. Simulations were performed to estimate the probability of target attainment for patients achieving target plasma colistin average steady-state concentrations (Css,avg). Results: A total of 334 plasma colistin concentrations were obtained from 79 pediatric patients with a median age (interquartile range) of 2.6 years (0.8−6.8 years); 73 (92.4%) were admitted to intensive care units. Colistin pharmacokinetics were adequately described by a one-compartment model with first-order elimination along with serum creatinine (SCr) as a significant covariate in colistin clearance. The simulation demonstrated that the recommended dose of 5 mg of colistin base activity (CBA)/kg/day resulted in 18.2−63.0% probability of achieving a target Css,avg of 2 mg/l. With a lower targeted Css,avg of 1 mg/l, colistin dosing with 7.5 mg and 5 mg of CBA/kg/day were adequate for children with SCr levels of 0.1−0.3 mg/dl and >0.3 mg/dl, respectively. Conclusions: SCr is a significant covariate in colistin clearance in children. Colistin dosing should be selected according to the patient's SCr level and the desired target Css,avg.http://www.sciencedirect.com/science/article/pii/S1201971221005397ColistinPharmacokineticsPediatricsMultidrug-resistant bacteria
spellingShingle Noppadol Wacharachaisurapol
Warumphon Sukkummee
Orawan Anunsittichai
Panida Srisan
Siriporn Sangkhamal
Prawat Chantharit
Warunee Punpanich Vandepitte
Thitima Wattanavijitkul
Thanyawee Puthanakit
Dose recommendations for intravenous colistin in pediatric patients from a prospective, multicenter, population pharmacokinetic study
International Journal of Infectious Diseases
Colistin
Pharmacokinetics
Pediatrics
Multidrug-resistant bacteria
title Dose recommendations for intravenous colistin in pediatric patients from a prospective, multicenter, population pharmacokinetic study
title_full Dose recommendations for intravenous colistin in pediatric patients from a prospective, multicenter, population pharmacokinetic study
title_fullStr Dose recommendations for intravenous colistin in pediatric patients from a prospective, multicenter, population pharmacokinetic study
title_full_unstemmed Dose recommendations for intravenous colistin in pediatric patients from a prospective, multicenter, population pharmacokinetic study
title_short Dose recommendations for intravenous colistin in pediatric patients from a prospective, multicenter, population pharmacokinetic study
title_sort dose recommendations for intravenous colistin in pediatric patients from a prospective multicenter population pharmacokinetic study
topic Colistin
Pharmacokinetics
Pediatrics
Multidrug-resistant bacteria
url http://www.sciencedirect.com/science/article/pii/S1201971221005397
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