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Verapamil stereoisomers during racemic verapamil administration: Effects of aging and comparisons to administration of individual stereoisomers
Author(s) -
Schwartz Janice B,
Capili Helen,
Wainer Irving W
Publication year - 1994
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1994.151
Subject(s) - verapamil , half life , medicine , enantiomer , pharmacology , pharmacokinetics , endocrinology , chemistry , calcium , organic chemistry
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 ~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. Clinical Pharmacology and Therapeutics (1994) 56, 368–376; doi: 10.1038/clpt.1994.151