Verapamil stereoisomers during racemic verapamil administration: effects of aging and comparisons to administration of individual stereoisomers

Clin Pharmacol Ther. 1994 Oct;56(4):368-76. doi: 10.1038/clpt.1994.151.

Abstract

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 approximately 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / metabolism*
  • Analysis of Variance
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Stereoisomerism
  • Verapamil / administration & dosage
  • Verapamil / pharmacokinetics*

Substances

  • Verapamil