Diurnal fluctuations in free and total plasma concentrations of valproic acid at steady state in epileptic patients

Roberto Riva, Fiorenzo Albani, Pietro Cortelli, Giuseppe Gobbi, Emilio Perucca, Agostino Baruzzi

Research output: Contribution to journalArticle

Abstract

The diurnal fluctuations in free and total plasma concentrations of valproic acid (VPA) were determined by taking serial blood samples at 2-h intervals in six epileptic patients receiving maintenance therapy with sodium valproate (9.6-24.0 mg/kg in three divided daily doses). Both the free and the total concentrations fluctuated markedly during the period examined (08001800 h). The fluctuation of the free drug was about twice as great as that of the total drug (79 ± 27% versus 47 ± 21%, p <0.01). There was a considerable inter- and intrapatient variability in free VPA fraction. In at least four of six patients the free fraction increased in proportion to the increase in total concentration. These findings are in line with available evidence that the binding of VPA to plasma proteins is saturable within the clinically occurring concentration range. The changing and unpredictable relationship between total and free concentration suggests that VPA therapy can be monitored more rationally by measuring the free drug.

Original languageEnglish
Pages (from-to)191-196
Number of pages6
JournalTherapeutic Drug Monitoring
Volume5
Issue number2
Publication statusPublished - 1983

Fingerprint

Valproic Acid
Plasmas
Pharmaceutical Preparations
Blood Proteins
Blood
Therapeutics

Keywords

  • Free fraction
  • Plasma concentrations
  • Valproic acid fluctuations

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Public Health, Environmental and Occupational Health

Cite this

Diurnal fluctuations in free and total plasma concentrations of valproic acid at steady state in epileptic patients. / Riva, Roberto; Albani, Fiorenzo; Cortelli, Pietro; Gobbi, Giuseppe; Perucca, Emilio; Baruzzi, Agostino.

In: Therapeutic Drug Monitoring, Vol. 5, No. 2, 1983, p. 191-196.

Research output: Contribution to journalArticle

@article{fcb1662dd2a14c9d823cb41e26d21cec,
title = "Diurnal fluctuations in free and total plasma concentrations of valproic acid at steady state in epileptic patients",
abstract = "The diurnal fluctuations in free and total plasma concentrations of valproic acid (VPA) were determined by taking serial blood samples at 2-h intervals in six epileptic patients receiving maintenance therapy with sodium valproate (9.6-24.0 mg/kg in three divided daily doses). Both the free and the total concentrations fluctuated markedly during the period examined (08001800 h). The fluctuation of the free drug was about twice as great as that of the total drug (79 ± 27{\%} versus 47 ± 21{\%}, p <0.01). There was a considerable inter- and intrapatient variability in free VPA fraction. In at least four of six patients the free fraction increased in proportion to the increase in total concentration. These findings are in line with available evidence that the binding of VPA to plasma proteins is saturable within the clinically occurring concentration range. The changing and unpredictable relationship between total and free concentration suggests that VPA therapy can be monitored more rationally by measuring the free drug.",
keywords = "Free fraction, Plasma concentrations, Valproic acid fluctuations",
author = "Roberto Riva and Fiorenzo Albani and Pietro Cortelli and Giuseppe Gobbi and Emilio Perucca and Agostino Baruzzi",
year = "1983",
language = "English",
volume = "5",
pages = "191--196",
journal = "Therapeutic Drug Monitoring",
issn = "0163-4356",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Diurnal fluctuations in free and total plasma concentrations of valproic acid at steady state in epileptic patients

AU - Riva, Roberto

AU - Albani, Fiorenzo

AU - Cortelli, Pietro

AU - Gobbi, Giuseppe

AU - Perucca, Emilio

AU - Baruzzi, Agostino

PY - 1983

Y1 - 1983

N2 - The diurnal fluctuations in free and total plasma concentrations of valproic acid (VPA) were determined by taking serial blood samples at 2-h intervals in six epileptic patients receiving maintenance therapy with sodium valproate (9.6-24.0 mg/kg in three divided daily doses). Both the free and the total concentrations fluctuated markedly during the period examined (08001800 h). The fluctuation of the free drug was about twice as great as that of the total drug (79 ± 27% versus 47 ± 21%, p <0.01). There was a considerable inter- and intrapatient variability in free VPA fraction. In at least four of six patients the free fraction increased in proportion to the increase in total concentration. These findings are in line with available evidence that the binding of VPA to plasma proteins is saturable within the clinically occurring concentration range. The changing and unpredictable relationship between total and free concentration suggests that VPA therapy can be monitored more rationally by measuring the free drug.

AB - The diurnal fluctuations in free and total plasma concentrations of valproic acid (VPA) were determined by taking serial blood samples at 2-h intervals in six epileptic patients receiving maintenance therapy with sodium valproate (9.6-24.0 mg/kg in three divided daily doses). Both the free and the total concentrations fluctuated markedly during the period examined (08001800 h). The fluctuation of the free drug was about twice as great as that of the total drug (79 ± 27% versus 47 ± 21%, p <0.01). There was a considerable inter- and intrapatient variability in free VPA fraction. In at least four of six patients the free fraction increased in proportion to the increase in total concentration. These findings are in line with available evidence that the binding of VPA to plasma proteins is saturable within the clinically occurring concentration range. The changing and unpredictable relationship between total and free concentration suggests that VPA therapy can be monitored more rationally by measuring the free drug.

KW - Free fraction

KW - Plasma concentrations

KW - Valproic acid fluctuations

UR - http://www.scopus.com/inward/record.url?scp=0020569483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020569483&partnerID=8YFLogxK

M3 - Article

C2 - 6410545

AN - SCOPUS:0020569483

VL - 5

SP - 191

EP - 196

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

IS - 2

ER -