Estimation of indocyanine green elimination rate constant k and retention rate at 15 min using patient age, weight, bilirubin, and albumin

Abstract

We sought to estimate the indocyanine green (ICG) clearance (Cl), the elimination rate constant (k), and the retention rate at 15 min (R (15)) using patient-specific covariates only. We analyzed plasma ICG concentration data at 5, 10, and 15 min after intravenous injection of 0.5 mg/kg of ICG and 17 kinds of patient-specific covariates in 1,276 patients using NONMEMA (R) (GloboMax LLC, Ellicott City, MD) for population pharmacokinetic modeling. The population models designed were externally validated on another dataset of 1,629 patients. The population typical value (TV) of Cl (Cl (TV)) and TV of volume of distribution (Vd (TV)) were modeled as: Cl (TV) (mL/min) = 117 x age (year)(-0.119) x body weight (kg)(0.348) x total bilirubin (mg/dL)(-0.226) x albumin (g/dL)(0.327). Vd (TV) (L) = 0.415 x body weight (kg)(0.596) x albumin (g/dL)(-0.292). ICG concentration at zero time (C (0)) and 15 min (C (15)) for R (15) (C (15)/C (0) x 100) were derived from following equations. C (0) = dose/Vd (TV) and C (15) = C (0)e(-k t) where t = 15 min and k = Vd (TV)/Cl (TV). Median percent prediction error and absolute prediction error in the estimated values were 18.0% and 25.6% for Cl; 6.1% and 16.5% for k; and -7.0% and 33.1% for R (15). The predictive performance of ICG k was better than those of ICG Cl and R (15).