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A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy.

ABSTRACT: The literature on the pharmacokinetics of vancomycin in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy is sparse. A population pharmacokinetic (PK) model for vancomycin in ECMO patients was developed using a nonlinear mixed effects modeling on the concentration-time profiles of 14 ECMO patients who received intravenous vancomycin. Model selection was based on log-likelihood criterion, goodness of fit plots, and scientific plausibility. Identification of covariates was done using a full covariate model approach. The pharmacokinetics of vancomycin was adequately described with a two-compartment model. Parameters included clearance of 2.83 L/hr, limited central volume of distribution 24.2 L, and low residual variability 0.67%. Findings from the analysis suggest that standard dosing recommendations for vancomycin in non-ECMO patients are adequate to achieve therapeutic trough concentrations in ECMO patients. This further shows that ECMO minimally affects the PK of vancomycin in adults including in higher-weight patients.

SUBMITTER: Moore JN

PROVIDER: S-EPMC5036424 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy.

Moore J N JN Healy J R JR Thoma B N BN Peahota M M MM Ahamadi M M Schmidt L L Cavarocchi N C NC Kraft W K WK

CPT: pharmacometrics & systems pharmacology 20160917 9

The literature on the pharmacokinetics of vancomycin in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy is sparse. A population pharmacokinetic (PK) model for vancomycin in ECMO patients was developed using a nonlinear mixed effects modeling on the concentration-time profiles of 14 ECMO patients who received intravenous vancomycin. Model selection was based on log-likelihood criterion, goodness of fit plots, and scientific plausibility. Identification of covariates was don ...[more]

PMID: 27639260

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Project description:Objective: Hemorrhagic and thromboembolic complications are common during support with extracorporeal membrane oxygenation (ECMO). As platelets play a pivotal role in hemostasis, we aimed to clarify how ECMO support affects platelet function. Methods: We included 33 adult patients undergoing ECMO support at a tertiary ECMO referral center at Aarhus University Hospital, Denmark. Blood samples were collected on the first morning following ECMO initiation, and subsequently every morning until the 7th (±1) day. Platelet aggregation was evaluated by whole blood impedance aggregometry (Multiplate® Analyzer) using adenosine diphosphate (ADPtest), arachidonic acid (ASPItest), and thrombin-receptor-agonist-peptide-6 (TRAPtest) as agonists. A new model was applied, taking platelet count into consideration in interpretation of impedance aggregometry analyses. On the 1st and 3rd day, platelet activation was assessed by flow cytometry (Navios) using collagen-related peptide, ADP, TRAP, and arachidonic acid as agonists. Results: Blood samples from all 33 patients were analyzed on day 1 of ECMO support; 24 patients were still receiving ECMO and analyzed on day 3; 12 patients were analyzed on day 7 (±1). After ECMO initiation, platelet counts decreased significantly (p < 0.002) and remained low during ECMO support. ECMO patients demonstrated significantly reduced platelet aggregation on day 1 compared with healthy controls (all p < 0.001). However, when taking platelet count into consideration, platelet aggregation relative to platelet count did not differ from healthy controls. Flow cytometry analyses demonstrated impaired platelet activation in ECMO patients on day 1 compared with healthy controls (all p < 0.03). No substantial difference was found in platelet activation from day 1 to day 3 on ECMO support. Conclusions: Employing impedance aggregometry and flow cytometry, we found both impaired platelet aggregation and decreased platelet activation on day 1 of ECMO support compared with healthy controls. However, platelet aggregation was not impaired, when interpreted relative to the low platelet counts. Furthermore, levels of bound fibrinogen, on the surface of activated platelets in ECMO patients, were higher than in healthy controls. Together, these findings suggestively oppose that platelets are universally impaired during ECMO support. No marked difference in activation from day 1 to day 3 was seen during ECMO support.

Dataset Information

A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy.

Publications

A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy.

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