The influence of free fatty acids on valproic acid plasma protein binding during fasting in normal humans

1982 ◽  
Vol 23 (4) ◽  
pp. 343-347 ◽  
Author(s):  
T. A. Bowdle ◽  
I. H. Patel ◽  
R. H. Levy ◽  
A. J. Wilensky
Keyword(s):  
Fatty Acids ◽  
Valproic Acid ◽  
Protein Binding ◽  
Free Fatty Acids ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Normal Humans

Inhibitory effect of free fatty acids on plasma protein binding of disopyramide in haemodialysis patients

1989 ◽  
Vol 36 (2) ◽  
pp. 175-180 ◽  
Author(s):  
T. Horiuchi ◽  
I. Johno ◽  
T. Hasegawa ◽  
S. Kitazawa ◽  
M. Goto ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Protein Binding ◽  
Free Fatty Acids ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Inhibitory Effect

Apparent Valproic Acid Neurotoxicity in a Hypoalbuminemic Patient

1993 ◽  
Vol 27 (1) ◽  
pp. 32-35 ◽  
Author(s):  
Barry E. Gidal ◽  
D. Michael Collins ◽  
Brad R. Beinlich
Keyword(s):  
Valproic Acid ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Plasma Concentrations ◽  
Free Fraction ◽  
Laboratory Evaluation ◽  
Neurologic Symptoms ◽  
Drug Concentrations ◽  
Dependent Protein

OBJECTIVE: To report a case of possible neurotoxicity caused by markedly elevated free valproic acid (VPA) plasma concentrations. CASE SUMMARY: A patient with a history of a mixed-type seizure disorder that had been treated with oral VPA 1000 mg four times daily for the previous two years was admitted to the neurology service with the chief complaint of increasing difficulty in walking and involuntary muscle jerks that were new in onset. The patient was hypersomnolent and dysarthric. The total plasma VPA concentration was 103 μg/mL, which was only slightly above the recommended therapeutic range (50–100 μg/mL). VPA free fraction and free plasma concentrations, however, were unexpectedly elevated (26 percent, 26.8 μg/mL, respectively). Further laboratory evaluation revealed a serum albumin concentration of 33 g/L. The neurologic symptoms resolved upon VPA dosage reduction. DISCUSSION: VPA displays concentration-dependent protein binding, resulting in disproportionate increases in drug free fraction with increasing drug concentration. This effect may be magnified in patients with decreased plasma protein-binding capacity. The plasma protein-binding kinetics of VPA are reviewed and the implications for therapeutic drug monitoring are discussed. CONCLUSIONS: It is likely that the markedly elevated free VPA plasma concentrations contributed to the neurologic symptoms displayed in this patient. In patients with decreased albumin concentrations, failure to recognize concentration-dependent protein binding, as well as exclusive reliance upon total drug concentrations, may lead to erroneous pharmacokinetic and therapeutic interpretations.

scholarly journals Plasma protein-binding and CSF concentrations of valproic acid in man following acute oral dosing.

1983 ◽  
Vol 16 (4) ◽  
pp. 365-369 ◽  
Author(s):  
WG Rapeport ◽  
AD Mendelow ◽  
G French ◽  
P MacPherson ◽  
E Teasdale ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Oral Dosing

Diurnal Oscillations in Plasma Protein Binding of Valproic Acid

Epilepsia ◽  
1982 ◽  
Vol 23 (3) ◽  
pp. 283-290 ◽  
Author(s):  
I. H. Patel ◽  
R. Venkataramanan ◽  
R. H. Levy ◽  
C. T. Viswanathan ◽  
L. M. Ojemann
Keyword(s):  
Valproic Acid ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein

In vivo plasma protein binding interaction between valproic acid and naproxen

1984 ◽  
Vol 9 (4) ◽  
pp. 359-363 ◽  
Author(s):  
Roberto Grimaldi ◽  
Sergio Lecchini ◽  
Francesca Crema ◽  
Emilio Perucca
Keyword(s):  
Valproic Acid ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Binding Interaction

Protein Binding of Valproic Acid in the Presence of Elevated Free Fatty Acids in Patient and Normal Human Serum

Epilepsia ◽  
1981 ◽  
Vol 22 (1) ◽  
pp. 11-17 ◽  
Author(s):  
C. L. Zimmerman ◽  
I. H. Patel ◽  
R. H. Levy ◽  
D. Edwards ◽  
S. D. Nelson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Valproic Acid ◽  
Protein Binding ◽  
Free Fatty Acids ◽  
Human Serum ◽  
Normal Human Serum ◽  
Normal Human
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