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.
Niwa
T
T
Product Development Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Tokuma
Y
Y
Nakagawa
K
K
Noguchi
H
H
Yamazoe
Y
Y
Kato
R
R
D001798:Blood Proteins / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008862:Microsomes, Liver / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism; D010084:Oxidation-Reduction
D001798:Blood Proteins; D002121:Calcium Channel Blockers; C035100:nilvadipine; D009543:Nifedipine