Abstract
The effects of altered albumin distribution on the apparent volume of distribution (V) and the apparent elimination rate constant (k) of drugs were investigated by a simulation analysis. The Equations derived by Øieet al. were modified for this purpose. Within the range observed in normal healthy subjects and patients, the change in albumin distribution significantly affectedV of drugs but, in general, notk. For drugs with more than 90% plasma-protein binding,V changed by more than 100%. The change in plasma-protein binding caused by an altered albumin distribution produced a greater effect onV than that caused by an altered albumin amount. These results suggest that albumin distribution is an important factor in controlling the kinetics of drugs which are highly bound to plasma protein. This is illustrated using midazolam as an example.
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Shimoda, M., Kokue, E., Hayama, T. et al. Effect of albumin distribution. Pharmaceutisch Weekblad Scientific Edition 11, 87–91 (1989). https://doi.org/10.1007/BF02110255
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DOI: https://doi.org/10.1007/BF02110255