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• W2334183818 abstract "The aim of the current study was to characterize the observed discrepancy between unbound plasma valproate (VPA) in single dose and steady state in humans. Unbound and total plasma VPA and subcutaneous microdialysate VPA concentrations were estimated in single dose (6 subjects, n = 33) and steady state (11 subjects, n = 110). Trough plasma samples from 14 patients with total VPA concentrations of 300 micromol/L and 14 patients with VPA concentrations ranging from 600 to 700 micromol/L were analyzed for the unbound VPA fraction and compared with the unbound VPA fraction in spiked plasma samples from healthy subjects containing similar total VPA concentrations. The unbound plasma VPA fraction was significantly higher (P < 0.001) in the steady-state group compared with the single-dose group. The unbound VPA fraction was significantly higher in steady state compared with spiked plasma samples at high and low total VPA concentrations (P < 0.001). The difference between microdialysate and unbound plasma VPA concentrations was significant in the steady-state group (P < 0.001), while no difference was observed in the single-dose group. The mean (+/- SD) subcutaneous microdialysate-to-unbound plasma ratio in the single-dose and steady-state groups was 1.08 (+/- 0.401) and 0.74 (+/- 0.123), respectively. The ratio difference between the groups was significant (P < 0.001). The results of the current study show that unbound plasma fractions of VPA are consistently higher in steady state compared with single dose. Together with the finding of higher unbound VPA fraction in steady state compared with spiked plasma samples, these results provide indirect evidence of displacement of VPA from plasma proteins by product(s) of VPA biotransformation. In addition, subcutaneous microdialysate VPA levels were consistently lower than unbound plasma levels in steady state but not after single dose. The mechanisms underlying this observation need to be studied further." @default.
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• W2334183818 date "2003-06-01" @default.
• W2334183818 modified "2023-10-12" @default.
• W2334183818 title "Unbound Valproate Fraction in Plasma and Subcutaneous Microdialysate in Steady State and After a Single Dose in Humans" @default.
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• W2334183818 doi "https://doi.org/10.1097/00007691-200306000-00020" @default.
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