Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/23248 |
Resumo: | Background: Meropenem is a carbapenem antibiotic commonly used in critically ill patients to treat severe infections. The available pharmacokinetic (PK) data has been mostly obtained from healthy volunteers as well as from clinical studies addressing selected populations, often excluding the elderly and also patients with renal failure. Our aim was to study PK of meropenem in a broader population of septic critically ill patients. Methods: We characterized the PK of meropenem in 15 critically ill patients during the first 36 hrs of therapy. Aditionally, whenever possible, we collected a second set of late plasma samples after 5 days of therapy to evaluate PK intra-patient variability and its correlation with clinical course. Patients received meropenem (1 g every 8 hrs IV). Drug plasma profiles were determined by high-performance liquid chromatography. The PK of meropenem was characterized and compared with clinical parameters. Results: Fifteen septic critically ill patients (8 male, median age 73 yrs) were included. The geometric mean of the volume of distribution at the steady state (V-ss)/weight was 0.20 (0.15-0.27) L/kg. No correlation of Vss/weight with severity or comorbidity scores was found. However the Sequential Organ Failure Assessment score correlated with the Vss/ weight of the peripheral compartment (r(2) = 0.55, p = 0.021). The median meropenem clearance (Cl) was 73.3 (45-120) mL/min correlated with the creatinine (Cr) Cl (r(2)=0.35, p = 0.033). After 5 days (N = 7) although Vss remained stable, a decrease in the proportion of the peripheral compartment (V-ss2) was found, from 61.3 (42.5-88.5)\% to 51.7 (36.6-73.1)\%. No drug accumulation was noted. Conclusions: In this cohort of septic, unselected, critically ill patients, large meropenem PK heterogeneity was noted, although neither underdosing nor accumulation was found. However, Cr Cl correlated to meropenem Cl and the Vss2 decreased with patient's improvement. |
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Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patientsAUGMENTED RENAL CLEARANCESEVERE INFECTIONSCONTROLLED-TRIALSEVERE SEPSISIntensive care unitSHOCKBETA-LACTAM CONCENTRATIONSPHARMACODYNAMICSMULTICENTERPharmacokineticsMeropenembeta-lactam antibioticsANTIBIOTIC-THERAPYVENTILATOR-ASSOCIATED PNEUMONIAMeropenembeta-lactam antibioticsPharmacokineticsIntensive care unitRM Therapeutics. PharmacologyRS Pharmacy and materia medicaBackground: Meropenem is a carbapenem antibiotic commonly used in critically ill patients to treat severe infections. The available pharmacokinetic (PK) data has been mostly obtained from healthy volunteers as well as from clinical studies addressing selected populations, often excluding the elderly and also patients with renal failure. Our aim was to study PK of meropenem in a broader population of septic critically ill patients. Methods: We characterized the PK of meropenem in 15 critically ill patients during the first 36 hrs of therapy. Aditionally, whenever possible, we collected a second set of late plasma samples after 5 days of therapy to evaluate PK intra-patient variability and its correlation with clinical course. Patients received meropenem (1 g every 8 hrs IV). Drug plasma profiles were determined by high-performance liquid chromatography. The PK of meropenem was characterized and compared with clinical parameters. Results: Fifteen septic critically ill patients (8 male, median age 73 yrs) were included. The geometric mean of the volume of distribution at the steady state (V-ss)/weight was 0.20 (0.15-0.27) L/kg. No correlation of Vss/weight with severity or comorbidity scores was found. However the Sequential Organ Failure Assessment score correlated with the Vss/ weight of the peripheral compartment (r(2) = 0.55, p = 0.021). The median meropenem clearance (Cl) was 73.3 (45-120) mL/min correlated with the creatinine (Cr) Cl (r(2)=0.35, p = 0.033). After 5 days (N = 7) although Vss remained stable, a decrease in the proportion of the peripheral compartment (V-ss2) was found, from 61.3 (42.5-88.5)\% to 51.7 (36.6-73.1)\%. No drug accumulation was noted. Conclusions: In this cohort of septic, unselected, critically ill patients, large meropenem PK heterogeneity was noted, although neither underdosing nor accumulation was found. However, Cr Cl correlated to meropenem Cl and the Vss2 decreased with patient's improvement.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNGonçalves-Pereira, JoãoSilva, Nuno ElvasMateus, AndréPinho, CatarinaPovoa, Pedro2017-09-14T22:01:09Z2014-04-142014-04-14T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article7application/pdfhttp://hdl.handle.net/10362/23248eng1471-2210PURE: 384380https://doi.org/10.1186/2050-6511-15-21info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:11:29Zoai:run.unl.pt:10362/23248Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:27:43.407317Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients |
title |
Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients |
spellingShingle |
Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients Gonçalves-Pereira, João AUGMENTED RENAL CLEARANCE SEVERE INFECTIONS CONTROLLED-TRIAL SEVERE SEPSIS Intensive care unit SHOCK BETA-LACTAM CONCENTRATIONS PHARMACODYNAMICS MULTICENTER Pharmacokinetics Meropenem beta-lactam antibiotics ANTIBIOTIC-THERAPY VENTILATOR-ASSOCIATED PNEUMONIA Meropenem beta-lactam antibiotics Pharmacokinetics Intensive care unit RM Therapeutics. Pharmacology RS Pharmacy and materia medica |
title_short |
Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients |
title_full |
Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients |
title_fullStr |
Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients |
title_full_unstemmed |
Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients |
title_sort |
Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients |
author |
Gonçalves-Pereira, João |
author_facet |
Gonçalves-Pereira, João Silva, Nuno Elvas Mateus, André Pinho, Catarina Povoa, Pedro |
author_role |
author |
author2 |
Silva, Nuno Elvas Mateus, André Pinho, Catarina Povoa, Pedro |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
dc.contributor.author.fl_str_mv |
Gonçalves-Pereira, João Silva, Nuno Elvas Mateus, André Pinho, Catarina Povoa, Pedro |
dc.subject.por.fl_str_mv |
AUGMENTED RENAL CLEARANCE SEVERE INFECTIONS CONTROLLED-TRIAL SEVERE SEPSIS Intensive care unit SHOCK BETA-LACTAM CONCENTRATIONS PHARMACODYNAMICS MULTICENTER Pharmacokinetics Meropenem beta-lactam antibiotics ANTIBIOTIC-THERAPY VENTILATOR-ASSOCIATED PNEUMONIA Meropenem beta-lactam antibiotics Pharmacokinetics Intensive care unit RM Therapeutics. Pharmacology RS Pharmacy and materia medica |
topic |
AUGMENTED RENAL CLEARANCE SEVERE INFECTIONS CONTROLLED-TRIAL SEVERE SEPSIS Intensive care unit SHOCK BETA-LACTAM CONCENTRATIONS PHARMACODYNAMICS MULTICENTER Pharmacokinetics Meropenem beta-lactam antibiotics ANTIBIOTIC-THERAPY VENTILATOR-ASSOCIATED PNEUMONIA Meropenem beta-lactam antibiotics Pharmacokinetics Intensive care unit RM Therapeutics. Pharmacology RS Pharmacy and materia medica |
description |
Background: Meropenem is a carbapenem antibiotic commonly used in critically ill patients to treat severe infections. The available pharmacokinetic (PK) data has been mostly obtained from healthy volunteers as well as from clinical studies addressing selected populations, often excluding the elderly and also patients with renal failure. Our aim was to study PK of meropenem in a broader population of septic critically ill patients. Methods: We characterized the PK of meropenem in 15 critically ill patients during the first 36 hrs of therapy. Aditionally, whenever possible, we collected a second set of late plasma samples after 5 days of therapy to evaluate PK intra-patient variability and its correlation with clinical course. Patients received meropenem (1 g every 8 hrs IV). Drug plasma profiles were determined by high-performance liquid chromatography. The PK of meropenem was characterized and compared with clinical parameters. Results: Fifteen septic critically ill patients (8 male, median age 73 yrs) were included. The geometric mean of the volume of distribution at the steady state (V-ss)/weight was 0.20 (0.15-0.27) L/kg. No correlation of Vss/weight with severity or comorbidity scores was found. However the Sequential Organ Failure Assessment score correlated with the Vss/ weight of the peripheral compartment (r(2) = 0.55, p = 0.021). The median meropenem clearance (Cl) was 73.3 (45-120) mL/min correlated with the creatinine (Cr) Cl (r(2)=0.35, p = 0.033). After 5 days (N = 7) although Vss remained stable, a decrease in the proportion of the peripheral compartment (V-ss2) was found, from 61.3 (42.5-88.5)\% to 51.7 (36.6-73.1)\%. No drug accumulation was noted. Conclusions: In this cohort of septic, unselected, critically ill patients, large meropenem PK heterogeneity was noted, although neither underdosing nor accumulation was found. However, Cr Cl correlated to meropenem Cl and the Vss2 decreased with patient's improvement. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-04-14 2014-04-14T00:00:00Z 2017-09-14T22:01:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/23248 |
url |
http://hdl.handle.net/10362/23248 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1471-2210 PURE: 384380 https://doi.org/10.1186/2050-6511-15-21 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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7 application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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