TY - JOUR
T1 - Plasma protein binding of drugs after severe burn injury
AU - Jeevendra Martyn, J. A.
AU - Abernethy, Darrell R.
AU - Greenblatt, David J.
PY - 1984/4
Y1 - 1984/4
N2 - Plasma protein binding in seven severely burned (35% to 85% of body) patients 1 to 25 days after burn injury was examined for two drugs: diazepam (DZ), which binds mainly to serum albumin (ALB), and imipramine (IMI), which binds primarily to α1-acid glycoprotein (AAG). Protein binding was determined by equilibrium dialysis, and AAG concentrations were measured by radial immunodiffusion. AAG concentrations increased from 36 to 99 mg/dl (day 1) to 221 to 268 mg/dl (days 5 to 20). The IMI free fraction values decreased from 11.2%-19.7% to 5.5%-7.8% and correlated well with AAG concentrations. IMI free fraction values were lower in burned patients (10.8% ± 0.8%) than in healthy controls (15.3% ± 0.7%). In contrast, DZ free fraction did not correlate with AAG or ALB concentrations. The DZ free fraction ranged from 1.5% to 8.04%, and changes in a given individual did not relate to time after injury. Free fraction of DZ was higher in the burned population (3.5% ± 0.37%) than in healthy controls (1.25% ± 0.05%). Basic drugs that are highly bound to AAG may show progressive, increased binding after burn injury, whereas drugs binding to ALB may decrease after burn injury. Such binding changes can alter the interpretation of total serum or plasma drug concentrations.
AB - Plasma protein binding in seven severely burned (35% to 85% of body) patients 1 to 25 days after burn injury was examined for two drugs: diazepam (DZ), which binds mainly to serum albumin (ALB), and imipramine (IMI), which binds primarily to α1-acid glycoprotein (AAG). Protein binding was determined by equilibrium dialysis, and AAG concentrations were measured by radial immunodiffusion. AAG concentrations increased from 36 to 99 mg/dl (day 1) to 221 to 268 mg/dl (days 5 to 20). The IMI free fraction values decreased from 11.2%-19.7% to 5.5%-7.8% and correlated well with AAG concentrations. IMI free fraction values were lower in burned patients (10.8% ± 0.8%) than in healthy controls (15.3% ± 0.7%). In contrast, DZ free fraction did not correlate with AAG or ALB concentrations. The DZ free fraction ranged from 1.5% to 8.04%, and changes in a given individual did not relate to time after injury. Free fraction of DZ was higher in the burned population (3.5% ± 0.37%) than in healthy controls (1.25% ± 0.05%). Basic drugs that are highly bound to AAG may show progressive, increased binding after burn injury, whereas drugs binding to ALB may decrease after burn injury. Such binding changes can alter the interpretation of total serum or plasma drug concentrations.
UR - http://www.scopus.com/inward/record.url?scp=0021277857&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021277857&partnerID=8YFLogxK
U2 - 10.1038/clpt.1984.73
DO - 10.1038/clpt.1984.73
M3 - Article
C2 - 6705453
AN - SCOPUS:0021277857
VL - 35
SP - 535
EP - 539
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 4
ER -