Stereoselective oxidation and plasma protein binding of nilvadipine, a new dihydropyridine calcium antagonist, in man.

The stereoselectivity in the plasma protein binding and oxidative metabolism of nilvadipine, a new dihydropyridine calcium antagonist, in man was studied. The free fraction values (fp) for the plasma protein binding of (+)- and (-)-nilvadipine determined by equilibrium dialysis were 1.00 and 0.90%, respectively; the fp of the (+)-nilvadipine was a little higher than that of the (-)-enantiomer. Marked differences between enantiomers were not observed in the blood to plasma ratio. On the other hand, Vmax/Km value, which is equivalent to the intrinsic clearance of the drug, for the oxidation of (+)-nilvadipine to the corresponding pyridine analogue by human liver microsomes was 0.43-0.54 times less than that for the oxidation of the (-)-enantiomer.