Studies of drug binding to plasma proteins using a variant of equilibrium dialysis.

摘要

The plasma protein binding of three model compounds was investigated using a variant of equilibrium dialysis, denoted comparative equilibrium dialysis (CED), and the results were compared with those obtained with ultrafiltration (UF). In CED, the buffer that the plasma is dialysed against in traditional equilibrium dialysis is replaced by, for example, plasma from other species. The CED method has the advantage that the unbound concentration (C(u)) does not need to be measured, which can be difficult for drugs with extremely small unbound fractions. Instead, the ratio of the total drug concentration (C(tot)) on either side of the dialysis membrane at equilibrium is a direct measure of the relative binding properties of the two plasma types. For the first model compound, having an unbound fraction (f(u)) of about 0.05% in human plasma, the time to reach equilibrium was too long (>/=40h) to make the CED technique feasible in practice. For the second model compound, the more weakly bound drug NAD-299 (with an unbound fraction of about 2% in human plasma), the CED equilibration times were considerably shortened (