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).


CONCLUSIONS
The predictive performance of ICG k was better than those of ICG Cl and R (15).
Kim
Ga Yeong
GY
Department of Laboratory Medicine, Korea University Medical Center, University of Korea College of Medicine, 126-1, Anam-dong, 5-Ga, Seongbuk-Gu, Seoul, 136-705, Republic of Korea. elimyh@amc.seoul.kr
Bae
Kyun Seop
KS
Noh
Gyu Jeong
GJ
Min
Won Ki
WK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001663:Bilirubin / Q000032:analysis*; D001835:Body Weight / Q000502:physiology; D005260:Female; D006801:Humans; D007208:Indocyanine Green / Q000032:analysis / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015233:Models, Statistical; D055815:Young Adult
D007208:Indocyanine Green; D001663:Bilirubin