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 rega rding effects of aging on clearance of individual verapamil enantiomer s. To determine effects of aging on elimination of S- and R-verapamil, racemic verapamil was infused to steady-state concentrations of simil ar 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; o ld, 60 to 81 years), and enantiomer concentrations were measured at ea ch steady-state and after infusions. S-Verapamil clearance was greater than R-verapamil clearance in all age groups (p < 0.001), and aging d ecreased 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 vera pamil concentration. A trend toward an age effect on elimination half- lives was seen (S-verapamil half-life, 281 +/- 116 versus 234 +/- 89 m inutes in elderly versus young; R-verapamil half-life, 253 +/- 56 vers us 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 o f both S- and R-verapamil during steady-state intravenous dosing of ra cemic verapamil with preserved stereoselective clearance of verapamil with aging.