Plasma protein binding of drugs after severe burn injury

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Abstract
Plasma protein binding in 7 severely burned (35-85% of body) patients 1-25 days after burn injury was examined for 2 drugs: diazepam (DZ), which binds mainly to serum albumin (ALB), and imipramine (IMI), which binds primarily to .alpha.1-acid glycoprotein (AAG). Protein binding was determined by equilibrium dialysis, and AAG concentrations were measured by radial immunodiffusion. AAG concentrations increased from 36-99 mg/dl (day 1) to 221-268 m/dl (days 5-20). 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%). DZ free fraction did not correlate with AAG or ALB concentrations. The DZ free fraction ranged from 1.5-8.04%, 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 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.

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