DISTRIBUTION OF DRUGS OVER WHOLE-BLOOD .1. THE TRANSPORT FUNCTION OF WHOLE-BLOOD FOR VALPROATE

  • 1 July 1989
    • journal article
    • research article
    • Vol. 11  (4) , 384-389
Abstract
A method is presented for the determination of valproate (VPA) in .apprx. 40 .mu.l erythrocyte concentrations. Valproate partition between plasma proteins, ultrafiltrate, and erythrocytes at various concentrations was studied in vitro and in vivo. Partition ratios depended on VPA concentration in whole blood and the ratio of erythrocytes/ultrafiltrate, which increased with rising concentrations in the ultrafiltrate fraction. Shifts in ratios were studied by expanding the ultrafiltrate fraction of VP-spiked blood. It appeared that VPA delivery to the expanded ultrafiltrate compartment originated in a disproportionately large part from erythrocytes. In vivo the half-life of VPA in the erythrocyte fraction was 0.7 h, whereas in the ultrafiltrate fraction and protein-bound fraction half-lives of 2 and 5 h were observed. It is concluded that for VPA in relation to erythrocytes a ''''last-come-first-go'''' system is plausible.

This publication has 4 references indexed in Scilit: