Hepatic drug clearance in children

Studies with indocyanine green as a model substrate

William E. Evans, Mary V. Relling, Siebold De Graaf, John H. Rodman, John A. Pieper, Michael Christensen, William R. Crom

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

For several drugs metabolized by the liver, higher dosages (mg/kg body weight) are required in children to attain serum concentrations comparable to those in adults. Indocyanine green (ICG), a commonly used model substrate for hepatic elimination of high intrinsic clearance drugs, has been extensively evaluated in adults but not in children. We evaluated the disposition of ICG in 115 children with leukemia and nine healthy adult volunteers. The mean (SD) ICG plasma clearance (CLP) for all 115 children (age 0.9—17.8 years) was significantly greater (p = 0.0006) than for adults [14.8 (7.8) versus 10.6 (2.4) mL/min/kg]. When clearances from only children <10 years of age (N = 85) were compared with those from adults, the difference was even greater [15.6 (7.3) versus 10.6 (2.4) mL/min/kg; p = 0.0001]. However, when ICG CLP was normalized to body surface area, values for children did not differ significantly from adults [378 (204) versus 422 (102) mL/min/m2]. These data provide insight as to why dosage (mg/kg) requirements of certain drugs are higher in children.

Original languageEnglish (US)
Pages (from-to)452-456
Number of pages5
JournalJournal of Pharmaceutical Sciences
Volume78
Issue number6
DOIs
StatePublished - Jan 1 1989

Fingerprint

Indocyanine Green
Liver
Pharmaceutical Preparations
Only Child
Body Surface Area
Healthy Volunteers
Leukemia
Body Weight
Serum

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Hepatic drug clearance in children : Studies with indocyanine green as a model substrate. / Evans, William E.; Relling, Mary V.; De Graaf, Siebold; Rodman, John H.; Pieper, John A.; Christensen, Michael; Crom, William R.

In: Journal of Pharmaceutical Sciences, Vol. 78, No. 6, 01.01.1989, p. 452-456.

Research output: Contribution to journalArticle

Evans, William E. ; Relling, Mary V. ; De Graaf, Siebold ; Rodman, John H. ; Pieper, John A. ; Christensen, Michael ; Crom, William R. / Hepatic drug clearance in children : Studies with indocyanine green as a model substrate. In: Journal of Pharmaceutical Sciences. 1989 ; Vol. 78, No. 6. pp. 452-456.
@article{cb48ce8a46fa48b792e7255ad0e62717,
title = "Hepatic drug clearance in children: Studies with indocyanine green as a model substrate",
abstract = "For several drugs metabolized by the liver, higher dosages (mg/kg body weight) are required in children to attain serum concentrations comparable to those in adults. Indocyanine green (ICG), a commonly used model substrate for hepatic elimination of high intrinsic clearance drugs, has been extensively evaluated in adults but not in children. We evaluated the disposition of ICG in 115 children with leukemia and nine healthy adult volunteers. The mean (SD) ICG plasma clearance (CLP) for all 115 children (age 0.9—17.8 years) was significantly greater (p = 0.0006) than for adults [14.8 (7.8) versus 10.6 (2.4) mL/min/kg]. When clearances from only children <10 years of age (N = 85) were compared with those from adults, the difference was even greater [15.6 (7.3) versus 10.6 (2.4) mL/min/kg; p = 0.0001]. However, when ICG CLP was normalized to body surface area, values for children did not differ significantly from adults [378 (204) versus 422 (102) mL/min/m2]. These data provide insight as to why dosage (mg/kg) requirements of certain drugs are higher in children.",
author = "Evans, {William E.} and Relling, {Mary V.} and {De Graaf}, Siebold and Rodman, {John H.} and Pieper, {John A.} and Michael Christensen and Crom, {William R.}",
year = "1989",
month = "1",
day = "1",
doi = "10.1002/jps.2600780605",
language = "English (US)",
volume = "78",
pages = "452--456",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - Hepatic drug clearance in children

T2 - Studies with indocyanine green as a model substrate

AU - Evans, William E.

AU - Relling, Mary V.

AU - De Graaf, Siebold

AU - Rodman, John H.

AU - Pieper, John A.

AU - Christensen, Michael

AU - Crom, William R.

PY - 1989/1/1

Y1 - 1989/1/1

N2 - For several drugs metabolized by the liver, higher dosages (mg/kg body weight) are required in children to attain serum concentrations comparable to those in adults. Indocyanine green (ICG), a commonly used model substrate for hepatic elimination of high intrinsic clearance drugs, has been extensively evaluated in adults but not in children. We evaluated the disposition of ICG in 115 children with leukemia and nine healthy adult volunteers. The mean (SD) ICG plasma clearance (CLP) for all 115 children (age 0.9—17.8 years) was significantly greater (p = 0.0006) than for adults [14.8 (7.8) versus 10.6 (2.4) mL/min/kg]. When clearances from only children <10 years of age (N = 85) were compared with those from adults, the difference was even greater [15.6 (7.3) versus 10.6 (2.4) mL/min/kg; p = 0.0001]. However, when ICG CLP was normalized to body surface area, values for children did not differ significantly from adults [378 (204) versus 422 (102) mL/min/m2]. These data provide insight as to why dosage (mg/kg) requirements of certain drugs are higher in children.

AB - For several drugs metabolized by the liver, higher dosages (mg/kg body weight) are required in children to attain serum concentrations comparable to those in adults. Indocyanine green (ICG), a commonly used model substrate for hepatic elimination of high intrinsic clearance drugs, has been extensively evaluated in adults but not in children. We evaluated the disposition of ICG in 115 children with leukemia and nine healthy adult volunteers. The mean (SD) ICG plasma clearance (CLP) for all 115 children (age 0.9—17.8 years) was significantly greater (p = 0.0006) than for adults [14.8 (7.8) versus 10.6 (2.4) mL/min/kg]. When clearances from only children <10 years of age (N = 85) were compared with those from adults, the difference was even greater [15.6 (7.3) versus 10.6 (2.4) mL/min/kg; p = 0.0001]. However, when ICG CLP was normalized to body surface area, values for children did not differ significantly from adults [378 (204) versus 422 (102) mL/min/m2]. These data provide insight as to why dosage (mg/kg) requirements of certain drugs are higher in children.

UR - http://www.scopus.com/inward/record.url?scp=0024954917&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024954917&partnerID=8YFLogxK

U2 - 10.1002/jps.2600780605

DO - 10.1002/jps.2600780605

M3 - Article

VL - 78

SP - 452

EP - 456

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 6

ER -