Population Pharmacokinetics of Caspofungin and Dose Simulations in Heart Transplant Recipients.

ABSTRACT

The effect of heart transplantation (HTx) on the pharmacokinetics (PK) of caspofungin is not well-characterized. The aim of this study was to investigate the population PK of caspofungin in HTx and non-HTx patients and to identify covariates that may affect the PK of caspofungin. Seven successive blood samples were collected before administration and at 1, 2, 6, 10, 16, and 24 h after the administration of caspofungin for at least 3 days. This study recruited 27 HTx recipients and 31 non-HTx patients with 414 plasma concentrations in total. A nonlinear mixed-effects model was used to describe the population PK of caspofungin. The PK of caspofungin was best described by a two-compartment model. The clearance (CL) and volume of the central compartment (Vc) of caspofungin were 0.385 liter/h and 4.27 liters, respectively. The intercompartmental clearance (Q) and the volume of the peripheral compartment (Vp) were 2.85 liters/h and 6.01 liters, respectively. In the final model, we found that albumin (ALB) affected the CL of caspofungin with an adjustment factor of -1.01, and no other covariates were identified. In this study, HTx was not found to affect the PK of caspofungin. Based on the simulations, the dose of caspofungin should be proportionately increased in patients with decreased ALB levels.