VERAPAMIL STEREOISOMERS DURING RACEMIC VERAPAMIL ADMINISTRATION - EFFECTS OF AGING AND COMPARISONS TO ADMINISTRATION OF INDIVIDUAL STEREOISOMERS

Aging decreases elimination of racemic verapamil but reports vary regarding effects of aging on clearance of individual verapamil enantiomers. To determine effects of aging on elimination of S- and R-verapamil, racemic verapamil was infused to steady-state concentrations of similar to 30, 60, and 120 ng/ml in 27 healthy subjects ranging in age from 23 to 81 years (young, 20 to 39 years; middle aged, 40 to 59 years; old, 60 to 81 years), and enantiomer concentrations were measured at each steady-state and after infusions. S-Verapamil clearance was greater than R-verapamil clearance in all age groups (p < 0.001), and aging decreased S-verapamil (p < 0.05) and R-verapamil (p < 0.008) clearance (average +/- SD, S-verapamil clearance was 14.3 +/- 4.7, 13.4 +/- 5.2, and 11.7 +/- 5.2 ml/min/kg; R-verapamil clearance was 6.5 +/- 3.3, 5.6 +/- 2.8, and 4.5 +/- 1.6 ml/min/kg in young, middle-aged, and older subjects, respectively). Enantiomer clearance was not effected by verapamil concentration. A trend toward an age effect on elimination half-lives was seen (S-verapamil half-life, 281 +/- 116 versus 234 +/- 89 minutes in elderly versus young; R-verapamil half-life, 253 +/- 56 versus 199 +/- 58 minutes in elderly versus young, p = 0.08). R- but not S-verapamil clearance during multistage infusions of racemic verapamil was lower than previously reported clearance after single intravenous enantiomer doses (p < 0.0001). In summary, aging decreases clearance of both S- and R-verapamil during steady-state intravenous dosing of racemic verapamil with preserved stereoselective clearance of verapamil with aging.