Premium
Valproic acid clearance: Unbound fraction and diurnal variation in young and elderly adults
Author(s) -
Bauer Larry A,
Davis Robin,
Wilensky Alan,
Raisys Vidmantas,
Levy Rene H
Publication year - 1985
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.1985.116
Subject(s) - valproic acid , diurnal temperature variation , fraction (chemistry) , circadian rhythm , variation (astronomy) , medicine , chemistry , chromatography , psychiatry , geography , epilepsy , meteorology , physics , astrophysics
Six young (22 to 25 years old) and six elderly (60 to 88 years old) healthy adults took valproic acid, 250 mg by mouth, at 8 AM and 8 PM for 5 days. On the fifth day, blood samples were drawn over each dosage interval. Both young and elderly subjects exhibited diurnal variability. Total and unbound clearances in the young and elderly subjects were about 10% and 15% higher during the evening. These changes led to lower total and unbound steady‐state and peak concentrations during the nighttime dosage interval. There were no differences in total steady‐state concentrations and kinetics computed from total concentrations between the young and elderly, but there were differences in unbound steady‐state concentrations and kinetics. Unbound clearances were 65% lower, which resulted in unbound steady‐state concentrations 67% higher in the elderly. The average unbound fractions in the elderly and young were 10.7% and 6.4%. To minimize the influence of diurnal variability, drug concentrations should be determined at the same time each day. Total valproic acid concentration data may be less useful in elderly patients; unbound concentrations may be more reliable in this population. Clinical Pharmacology and Therapeutics (1985) 37 , 697–700; doi: 10.1038/clpt.1985.116