Population Pharmacokinetics of Caspofungin among Extracorporeal Membrane Oxygenation Patients during the Postoperative Period of Lung Transplantation

Abstract

Background:Little is known about the influence of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of caspofungin. The aim of this study was to describe population PK of caspofungin in patients with and without ECMO during the postoperative period of lung transplantation (LTx) and investigate covariates influencing caspofungin PK. Methods:We compared ECMO patients with non-ECMO patients, and patients before and after ECMO weaning as self-controls, to analyzed changes in caspofungin PK. Eight serial blood samples were collected from each patient for PK analysis. The population PK of caspofungin was described using non-linear mixed effects modeling. Results:Twelve ECMO and 7 non-ECMO lung transplant recipients were enrolled in this study .None of patients received renal replacement therapy during any part of the study period. The PK of caspofungin was best described by a two-compartment model. There were no significant difference in the PK parameters and concentrations of caspofungin among the ECMO, non-ECMO, and self-control group. In the final covariate model, we found that there was a significant association between the male gender and increased distribution volume, that a higher Sequential Organ Failure Assessment score was related to an increase in intercompartmental clearance, and that a longer operative time was related to an increase in clearance and the volume of distribution. Conclusion:ECMO did not have a significant impact on the PK of caspofungin in patients after LTx. Some factors were identified as statistically significant covariates related to the PK of caspofungin ; however, their impact on clinical practice of caspofungin needs to be investigated further in more studies.

Population Pharmacokinetics of Caspofungin and Dose Simulations in Heart Transplant Recipients

“…We also examined ECMO as a covariate and found no significant effect of ECMO on the PK of caspofungin. The same conclusion was reached by a previous study ( 38 ) by Wang et al, who investigated the PK of caspofungin in lung transplant recipients on ECMO therapy. This is potentially attributable to the fact that the ECMO circuit may not sequester caspofungin in vivo .…”

Effects of ex vivo Extracorporeal Membrane Oxygenation Circuits on Sequestration of Antimicrobial Agents

“…A case report (22) observed that the standard dose of caspofungin failed to reach the target plasma concentration level during ECMO support. However, other in vivo studies (23)(24)(25) have suggested that ECMO does not affect the pharmacokinetic characteristics of caspofungin. Caspofungin is hydrophilic (log P −2.798) but has a high protein binding rate (97%), which may lead to significant differences in its recovery in different types of ECMO circuits.…”

Development and Quality Control of a Population Pharmacokinetic Model Library for Caspofungin

“…Three studies enrolled a pediatric population between three months and 18 years, while the rest included adults only. Five studies focused on transplant patients, including allogeneic hematopoietic stem cell transplant [ 25 , 32 ], heart transplant [ 29 ], lung transplant [ 30 ], and liver transplant [ 26 ]. While most studies collected only plasma concentrations, Pressiat et al [ 26 ] collected plasma and peritoneal fluid samples.…”