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 language | English |
|---|---|
| Pages (from-to) | 191-196 |
| Number of pages | 6 |
| Journal | Therapeutic Drug Monitoring |
| Volume | 5 |
| Issue number | 2 |
| Publication status | Published - 1983 |
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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 journal › Article
}
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
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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 -