Relationship between alpha 1-acid glycoprotein and distribution of disopyramide and mono-N-dealkyldisopyramide in whole blood.

The binding of disopyramide (DP) and mono-N-dealkyldisopyramide (MND) was measured by equilibrium dialysis in spiked whole blood (10 mumol l-1 DP or MND) from 50 patients having a serum concentration of alpha 1-acid glycoprotein (AAG) ranging from 0.40 to 3.14 g l-1, as well as in whole blood from five healthy subjects, spiked with different concentrations of AAG ranging from 0.61 to 3.33 g l-1. The binding ratio (moles bound divided by moles unbound) in all samples increased from 1.0 to 8.0 for DP and 0.6 to 3.3 for MND with increasing AAG concentrations. The binding varied according to the AAG concentrations both in patients and healthy subjects. Similarly total and free plasma concentrations of DP and MND were also measured. With increasing AAG concentrations the total concentrations measured increased from 9.0 to 15.9 mumol l-1 for DP and from 6.8 to 11.8 mumol l-1 for MND whereas the free concentrations decreased from 3.8 to 0.5 mumol l-1 for DP and from 5.0 to 2.0 mumol l-1 for MND. With increasing AAG concentrations the whole blood/plasma concentration ratio decreased from 1.11 and 1.47 to 0.63 and 0.85 for DP and MND respectively. The ratio between their concentration in cells and the unbound concentration in plasma, however, was constant over the whole AAG concentration range. The mean ratios for all samples were 3.0 and 3.1 for DP and MND respectively, indicating that both compounds are bound or distributed to the blood cells. The distribution of the drugs in whole blood changed according to increasing AAG concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)