THE EFFECTS OF AGE AND GENDER ON THE STEREOSELECTIVE PHARMACOKINETICS OF VERAPAMIL

The effects of age and gender on the pharmacokinetics of verapamil stereoisomers were examined. Eighty milligrams of racemic verapamil was given orally to 12 young and 12 elderly healthy subjects, half of whom were women. The area under the plasma concentration-time curves (AUC) of (S)- and (R)-verapamil were greater in the elderly group than in the young group [(S)-/(R)-verapamil (mean +/-SD), 214.4 +/- 123.0/1582.2 +/- 763.0 and 50.4 +/- 36.5/584.9 +/- 252.4 ng . hr/ml for the elderly and young groups, respectively (p < 0.001/p < 0.001)]. Conversely, the apparent oral clearance values of (S)-and (R) -verapamil were significantly smaller in the elderly group than in the young group [(S)-/(R)-verapamil (mean +/- SD), 4.8 +/- 3.0/0.53 +/- 0.21 and 22.5 +/- 21.3/1.30 +/- 0.67 L/hr/kg for the elderly and young groups, respectively (p < 0.01/p < 0.001)]. The ratio of apparent oral clearance of (S)- to (R)-verapamil was significantly smaller in the elderly group than in the young group. As a consequence, the negative chronotropic and dromotropic effect of verapamil was observed in the elderly group. This study suggests that the effect of age on metabolism was greater for (S)-verapamil than for (R)-verapamil.