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Diurnal variation in valproic acid clearance
Author(s) -
Bauer Larry A,
Davis Robin,
Wilensky Alan,
Raisys Vidmantas,
Levy Rene H
Publication year - 1984
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.1984.68
Subject(s) - evening , valproic acid , morning , diurnal temperature variation , chemistry , circadian rhythm , zoology , clinical pharmacology , steady state (chemistry) , pharmacology , endocrinology , medicine , epilepsy , biology , physics , atmospheric sciences , astronomy , psychiatry , geology
Diurnal variation in total and unbound valproic acid concentrations was measured at steady state in seven healthy men and three healthy women after 250‐mg oral doses every 12 hr. Total average steady‐state concentration (C ss ) during the morning dosage interval was 50.4 mg/l. During the evening dosage interval, total C ss was 45.7 mg/l. Unbound C ss was also less during the evening (2.9 and 3.4 mg/l). These changes were due to higher total and unbound clearance rates during the evening dosage interval. Total peak concentrations were lower (56.8 and 64.3 mg/l) and time of peak concentrations slightly longer (2.2 and 1.8 hr) during the evening. There was marked inter individual variability in all these changes. For best reproducibility of steady‐state valproic acid concentrations, our results suggest that total and unbound levels be drawn at the same time of day. Clinical Pharmacology and Therapeutics (1984) 35, 505–509; doi: 10.1038/clpt.1984.68