Binding of prazosin and propranolol at variable alpha 1-acid glycoprotein and albumin concentrations.
1. The effect of variable alpha 1-acid glycoprotein (AAG) and albumin (HSA) concentrations on the binding of prazosin and propranolol was assessed in plasma after surgery and in mixtures of AAG/HSA with concentrations mimicking those found in vivo. 2. On the pre-operative day the binding of prazosin and propranolol was 94.8% and 89.0%, respectively and 97.3% and 93.2%, respectively, 5 days after surgery. 3. In solutions containing mixtures of highly purified AAG and HSA representing the pre-operative state, 88.6% and 83.9% binding of prazosin and propranolol was observed, whereas for solutions mimicking post-operative plasma, the equivalent values were 94.6% and 91.4%, respectively. 4. The ratios between bound and unbound concentrations of both drugs were closely correlated to the concentrations of AAG, but not to the concentrations of HSA. 5. The present study demonstrates that AAG is responsible for the binding variability of prazosin and propranolol in plasma from post-operative patients.
Sager
G
G
Department of Pharmacology, University of Tromsø, Norway.
Jaeger
R
R
Little
C
C
D000368:Aged; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009961:Orosomucoid / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism*; D011433:Propranolol / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*
D009961:Orosomucoid; D012709:Serum Albumin; D011433:Propranolol; D011224:Prazosin