Postburn serum drug binding and serum protein concentrations

Area of Science:

• Pharmacology
• Biochemistry
• Clinical Medicine

Background:

• Drug efficacy and toxicity are influenced by unbound (free) drug concentrations in serum.
• Burn injuries significantly alter physiological parameters, potentially affecting drug pharmacokinetics.

Purpose of the Study:

• To investigate the impact of burn injury on the serum free fractions of various drugs.
• To correlate changes in drug free fractions with alterations in serum protein levels.

Main Methods:

• Determined serum free fractions of diazepam, imipramine, lidocaine, meperidine, phenytoin, propranolol, and salicylic acid in burn patients.
• Measured serum protein fractions via electrophoresis and alpha-1 acid glycoprotein levels.
• Compared drug free fractions and protein levels to control subjects at one and four weeks post-burn.

Main Results:

• Albumin-bound drug free fractions (diazepam, phenytoin, salicylic acid) were elevated one week post-burn due to decreased albumin levels.
• Alpha-1 acid glycoprotein-bound drug free fractions (imipramine, lidocaine, meperidine, propranolol) were decreased one week post-burn due to increased alpha-1 acid glycoprotein levels.
• Altered free fractions for some drugs persisted at four weeks post-burn.

Conclusions:

• Burn injury causes significant alterations in drug binding, affecting the free fractions of commonly used medications.
• These changes in drug free fractions are linked to dynamic shifts in serum albumin and alpha-1 acid glycoprotein concentrations.
• Understanding these pharmacokinetic changes is crucial for optimizing drug therapy in burn patients.