PMID: 6401631Feb 1, 1983Paper

Free fraction of valproic acid: in vitro time-dependent increase and correlation with free fatty acid concentration in human plasma and serum

Epilepsia
F AlbaniE Perucca

Abstract

The effect of sample incubation and storage on the protein binding of the antiepileptic drug valproic acid (VPA) and on the concentration of free fatty acids (FFA) was investigated in serum and plasma collected from four normal volunteers. Both the free fraction of VPA and the concentration of FFA increased progressively with time when samples were incubated at 4 to 37 degrees C. These effects occurred to the same extent in both serum and heparinized plasma. At 4 degrees C and at room temperature, the increase in free drug fraction was relatively small (18 and 25% respectively at 24 h), whereas at 37 degrees C it was quite considerable (24% at 8 h and 40% at 24 h). At room temperature, FFA rose on average by 22% at 4 h, 34% at 8 h, and 86% at 24 h, whereas at 37 degrees C the increases at the same incubation times were 59, 90, and 160%, respectively. There was a strong positive relationship between changes in free VPA fraction and FFA content of the samples. The time-dependent changes in VPA binding capacity described in this study may lead to overestimation of the actual free concentration in vivo, especially when this is estimated by equilibrium dialysis or ultracentrifugation techniques requiring long incubation (centrifugat...Continue Reading

References

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Citations

Oct 1, 1984·European Journal of Drug Metabolism and Pharmacokinetics·R GrimaldiE Perucca
Jan 1, 1991·Life Sciences·D Cotariu, J L Zaidman
Sep 1, 1988·The Japanese Journal of Psychiatry and Neurology·T MiharaM Seino
May 1, 1994·Epilepsia·B GuldvogH Bjørnaes
Oct 1, 1993·Brain Pathology·H K Wolf, O D Wiestler
Jul 1, 1995·Journal of Neurology, Neurosurgery, and Psychiatry·M R NewtonP F Bladin
May 26, 2004·Neurosurgery·Joseph R SmithKostas Fountas
Apr 1, 1996·Journal of Pharmaceutical Sciences·P W SlattumK L Brouwer
May 3, 2005·Journal of Pharmaceutical and Biomedical Analysis·Andrzej L Dawidowicz, Rafal Kalitynski
Oct 1, 1983·British Journal of Clinical Pharmacology·W G RapeportM J Brodie
Jan 1, 1985·Biopharmaceutics & Drug Disposition·M BialerF Pachys
Jun 1, 1984·British Journal of Clinical Pharmacology·F AlbaniE Perucca
Jun 1, 1984·British Journal of Clinical Pharmacology·E PeruccaG M Frigo
Mar 29, 2003·Paediatric Drugs·Jamie T GilmanAna E Campo
Oct 16, 2012·Clinica Chimica Acta; International Journal of Clinical Chemistry·Fan ShenSongmei Liu
May 1, 1985·Pharmacotherapy·E M Rimmer, A Richens

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