Zinc unbound concentration as an anchor to drive individualize repletion.

BACKGROUND AND AIMS: Zinc (Zn) quantification is of particular interest in many clinical condition (e.g. inflammatory disease, critical care). Currently, Zn status is assessed by measuring plasma/serum concentration. This concentration corresponds to the sum of unbound Zn (Zn-Cu) and Zn highly bound to albumin (Zn-Cb). METHODS: Using a pharmacokinetic approach to the interpretation of total Zn concentration (Zn-Ct), taking into account Zn-Cu and the influence of hypoalbuminemia on Zn-Cb, it is possible to improve the individualization of Zn repletion. RESULTS: Therefore, during pregnancy and in certain inflammatory disease situations, repletion may not be necessary. However, as in critical care, it would be more appropriate to perform Zn-Cu assays to improve Zn repletion. CONCLUSION: Coupled total and unbound Zn should be monitored in order to individualize Zn repletion.

Antiretroviral unbound concentration during pregnancy: piece of interest in the puzzle?

Atazanavir and darunavir total concentrations (drug bound to plasma proteins plus unbound drug) progressively decrease during pregnancy. This pharmacokinetic variation leads physicians to recommend increasing doses. Conversely, the unbound concentration (Cu), i.e. the pharmacologically active form of the drug, remains unchanged. The explanation of this desynchronization lies in the fact that the clearance of the unbound form, corresponding to the intrinsic metabolic capacity of the hepatocytes, is the only factor driving Cu, and is constant during pregnancy. The attention of HIV physicians should be attracted to this aspect of pharmacokinetics, which is often incompletely understood and could lead to inadequate dose adjustment, which could then cause overexposure of the foetus for many months, with unknown consequences.