Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation
Objectives: This study aimed to develop a piperacillin population PK model for critically ill Brazil-ian patients and describe interethnic variation using an external validation. Methods: Plasma samples were obtained from 24 ICU patients during the fifth day of piperacillin treatment and assayed by...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/4/434 |
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| author | Cristina Sanches Geisa C. S. Alves Andras Farkas Samuel Dutra da Silva Whocely Victor de Castro Farah Maria Drummond Chequer Francisco Beraldi-Magalhães Igor Rafael dos Santos Magalhães André de Oliveira Baldoni Mark D. Chatfield Jeffrey Lipman Jason A. Roberts Suzanne L. Parker |
| author_facet | Cristina Sanches Geisa C. S. Alves Andras Farkas Samuel Dutra da Silva Whocely Victor de Castro Farah Maria Drummond Chequer Francisco Beraldi-Magalhães Igor Rafael dos Santos Magalhães André de Oliveira Baldoni Mark D. Chatfield Jeffrey Lipman Jason A. Roberts Suzanne L. Parker |
| author_sort | Cristina Sanches |
| collection | DOAJ |
| description | Objectives: This study aimed to develop a piperacillin population PK model for critically ill Brazil-ian patients and describe interethnic variation using an external validation. Methods: Plasma samples were obtained from 24 ICU patients during the fifth day of piperacillin treatment and assayed by HPLC-UV. Population pharmacokinetic modelling was conducted using Pmetrics. Empiric dose of 4 g IV 6- and 8-hourly were simulated for 50 and 100% <i>f</i>T > MIC and the probabil-ity of target attainment (PTA) and the fractional target attainment (FTA) determined. Results: A two-compartment model was designed to describe the pharmacokinetics of critically ill Brazillian patients. Clearance and volume of distribution were (mean ± SD) 3.33 ± 1.24 L h<sup>−1</sup> and 10.69 ± 4.50 L, respectively. Creatinine clearance was positively correlated with piperacillin clearance and a high creatinine clearance was associated with lower values of PTA and FTA. An external vali-dation was performed using data from two different ethnic ICU populations (<i>n</i> = 30), resulting in acceptable bias and precision. Conclusion: The primary pharmacokinetic parameters obtained from critically ill Brazilian patients were similar to those observed in studies performed in critically ill patients of other ethnicities. Based on our results, the use of dose adjustment based on creati-nine clearance is required in Brazilian patients. |
| first_indexed | 2024-03-09T11:15:43Z |
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| language | English |
| last_indexed | 2024-03-09T11:15:43Z |
| publishDate | 2022-03-01 |
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| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-3bce168c29e04319bfb1676ded4465af2023-12-01T00:31:42ZengMDPI AGAntibiotics2079-63822022-03-0111443410.3390/antibiotics11040434Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External ValidationCristina Sanches0Geisa C. S. Alves1Andras Farkas2Samuel Dutra da Silva3Whocely Victor de Castro4Farah Maria Drummond Chequer5Francisco Beraldi-Magalhães6Igor Rafael dos Santos Magalhães7André de Oliveira Baldoni8Mark D. Chatfield9Jeffrey Lipman10Jason A. Roberts11Suzanne L. Parker12Campus Centro Oeste, Universidade Federal de Sao Joao del Rei, Divinopolis 35501-296, BrazilCampus Centro Oeste, Universidade Federal de Sao Joao del Rei, Divinopolis 35501-296, BrazilOptimum Dosing Strategies, Bloomingdale, NJ 07403, USACampus Centro Oeste, Universidade Federal de Sao Joao del Rei, Divinopolis 35501-296, BrazilCampus Centro Oeste, Universidade Federal de Sao Joao del Rei, Divinopolis 35501-296, BrazilCampus Centro Oeste, Universidade Federal de Sao Joao del Rei, Divinopolis 35501-296, BrazilPrograma de Pós Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus 69040-000, BrazilFaculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Manaus 69077-000, BrazilCampus Centro Oeste, Universidade Federal de Sao Joao del Rei, Divinopolis 35501-296, BrazilUniversity of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, AustraliaUniversity of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, AustraliaUniversity of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, AustraliaUniversity of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, AustraliaObjectives: This study aimed to develop a piperacillin population PK model for critically ill Brazil-ian patients and describe interethnic variation using an external validation. Methods: Plasma samples were obtained from 24 ICU patients during the fifth day of piperacillin treatment and assayed by HPLC-UV. Population pharmacokinetic modelling was conducted using Pmetrics. Empiric dose of 4 g IV 6- and 8-hourly were simulated for 50 and 100% <i>f</i>T > MIC and the probabil-ity of target attainment (PTA) and the fractional target attainment (FTA) determined. Results: A two-compartment model was designed to describe the pharmacokinetics of critically ill Brazillian patients. Clearance and volume of distribution were (mean ± SD) 3.33 ± 1.24 L h<sup>−1</sup> and 10.69 ± 4.50 L, respectively. Creatinine clearance was positively correlated with piperacillin clearance and a high creatinine clearance was associated with lower values of PTA and FTA. An external vali-dation was performed using data from two different ethnic ICU populations (<i>n</i> = 30), resulting in acceptable bias and precision. Conclusion: The primary pharmacokinetic parameters obtained from critically ill Brazilian patients were similar to those observed in studies performed in critically ill patients of other ethnicities. Based on our results, the use of dose adjustment based on creati-nine clearance is required in Brazilian patients.https://www.mdpi.com/2079-6382/11/4/434piperacillinpharmacokineticscritically illethnic groupantimicrobial |
| spellingShingle | Cristina Sanches Geisa C. S. Alves Andras Farkas Samuel Dutra da Silva Whocely Victor de Castro Farah Maria Drummond Chequer Francisco Beraldi-Magalhães Igor Rafael dos Santos Magalhães André de Oliveira Baldoni Mark D. Chatfield Jeffrey Lipman Jason A. Roberts Suzanne L. Parker Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation Antibiotics piperacillin pharmacokinetics critically ill ethnic group antimicrobial |
| title | Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation |
| title_full | Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation |
| title_fullStr | Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation |
| title_full_unstemmed | Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation |
| title_short | Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation |
| title_sort | population pharmacokinetic model of piperacillin in critically ill patients and describing interethnic variation using external validation |
| topic | piperacillin pharmacokinetics critically ill ethnic group antimicrobial |
| url | https://www.mdpi.com/2079-6382/11/4/434 |
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