Effect of heparin on digitoxin protein binding

Area of Science:

• Pharmacology
• Clinical Chemistry

Background:

• Heparin administration has been anecdotally linked to reduced digitoxin binding to plasma proteins.
• This phenomenon raises questions about whether the effect is an in vivo alteration or an artifact of blood collection and in vitro processes.

Purpose of the Study:

• To investigate whether heparin affects digitoxin protein binding in vivo or if the effect is solely due to in vitro heparin-induced lipolysis.
• To clarify the mechanism behind previously reported reductions in digitoxin-plasma protein binding.

Main Methods:

• Studied 10 patients on digitoxin maintenance therapy undergoing hemodialysis.
• Measured digitoxin free fraction before and after heparin administration, with and without inhibition of in vitro lipolysis using diethyl p-nitrophenyl phosphate.
• Assessed digitoxin salivary levels as an indicator of unbound drug.

Main Results:

• Digitoxin free fraction increased post-heparin (2.5% to 4.4%), but this increase was abolished when in vitro lipolysis was inhibited (2.3% to 2.4%).
• Digitoxin salivary levels remained unchanged after heparin administration.
• These findings indicate heparin does not alter digitoxin protein binding in vivo.

Conclusions:

• The previously observed reduction in digitoxin protein binding following heparin administration is an artifact of in vitro lipolysis, not an in vivo effect.
• Heparin does not significantly alter the in vivo binding of digitoxin to plasma proteins.