PMID: 12766568May 27, 2003Paper

Unbound valproate fraction in plasma and subcutaneous microdialysate in steady state and after a single dose in humans

Therapeutic Drug Monitoring
Martin LindbergerLars Ståhle

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-s...Continue Reading

References

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Jun 19, 1998·Therapeutic Drug Monitoring·M LindbergerL Ståhle

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