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Assessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patients

2014-04-14Artigo científico Acesso aberto
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dc.contributor.authorGonçalves-Pereira, João
dc.contributor.authorGonçalves-Pereira, João
dc.contributor.authorSilva, Nuno Elvas
dc.contributor.authorMateus, André
dc.contributor.authorPinho, Catarina
dc.contributor.authorPóvoa, Pedro
dc.contributor.authorPovoa, Pedro
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.pblBioMed Central (BMC)
dc.date.accessioned2017-09-14T22:01:09Z
dc.date.available2017-09-14T22:01:09Z
dc.date.issued2014-04-14
dc.description.abstractBackground: 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent7
dc.format.extent359997
dc.identifier.doi10.1186/2050-6511-15-21
dc.identifier.issn1471-2210
dc.identifier.otherPURE: 384380
dc.identifier.otherPURE UUID: 8b5b8242-fe78-4b39-8475-2b4a6613a456
dc.identifier.otherresearchoutputwizard: 45565
dc.identifier.otherPubMed: 24731745
dc.identifier.otherWOS: 000335250100001
dc.identifier.otherScopus: 84906930024
dc.identifier.urihttp://hdl.handle.net/10362/23248
dc.language.isoeng
dc.peerreviewedyes
dc.subjectAUGMENTED RENAL CLEARANCE
dc.subjectSEVERE INFECTIONS
dc.subjectCONTROLLED-TRIAL
dc.subjectSEVERE SEPSIS
dc.subjectIntensive care unit
dc.subjectSHOCK
dc.subjectBETA-LACTAM CONCENTRATIONS
dc.subjectPHARMACODYNAMICS
dc.subjectMULTICENTER
dc.subjectPharmacokinetics
dc.subjectMeropenem
dc.subjectbeta-lactam antibiotics
dc.subjectANTIBIOTIC-THERAPY
dc.subjectVENTILATOR-ASSOCIATED PNEUMONIA
dc.subjectMeropenem
dc.subjectbeta-lactam antibiotics
dc.subjectPharmacokinetics
dc.subjectIntensive care unit
dc.subjectRM Therapeutics. Pharmacology
dc.subjectRS Pharmacy and materia medica
dc.titleAssessment of pharmacokinetic changes of meropenem during therapy in septic critically ill patientsen
dc.typejournal article
degois.publication.firstPage
degois.publication.issueNA
degois.publication.lastPage
degois.publication.titleBMC Pharmacology
degois.publication.volume15
dspace.entity.typePublication
person.familyNameGonçalves-Pereira
person.familyNamePovoa
person.givenNameJoão
person.givenNamePedro
person.identifier1693343
person.identifier.ciencia-id2C13-C2A3-79E7
person.identifier.ciencia-id0C16-5CF9-9238
person.identifier.orcid0000-0002-7538-3777
person.identifier.orcid0000-0002-7069-7304
person.identifier.scopus-author-id6602772147
rcaap.rightsopenAccess
relation.isAuthorOfPublicationc17ef000-d96c-4979-93f9-ce6e14b79a54
relation.isAuthorOfPublication04ec38ba-be1e-46e5-8007-0e65a557d0f4
relation.isAuthorOfPublication.latestForDiscoveryc17ef000-d96c-4979-93f9-ce6e14b79a54

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