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

Background: 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.

Methods: 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 NONMEM (GloboMax LLC, Ellicott City, MD) for population pharmacokinetic modeling. The population models designed were externally validated on another dataset of 1,629 patients.

Results: 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 = Cl (TV)/Vd (TV). [corrected] 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).

Conclusion: The predictive performance of ICG k was better than those of ICG Cl and R (15).