Fig. 3.

Concentration–time profiles for different dosing regimens that have been used in the treatment of early ARDS. Glucocorticoid average plasma concentrations were simulated on the basis of published pharmacokinetic parameters for hydrocortisone (HC), methylprednisolone (MP) and dexamethasone (DX) and converted to MP equivalent concentrations using their reported relative receptor affinity (RRA) and fraction unbound to plasma proteins (f_u) [8, 9]. Pharmacokinetic parameters used for the simulations were as previously described: Clearance 18, 21, and 17 L/h; volume of distribution 33, 64, and 103 L for HC, MP and DX, respectively. The conversion to MP equivalent concentrations for HC and DX was performed according to the relationship: MP equivalent plasma concentration = HC or DX concentration × (f_{u,HC or DX}/f_u,MP) × (RRA_{HC or DX}/RRA_MP). The applied value for RRA and f_u were 9, 42, 100 and 0.20, 0.23, 0.32 for HC, MP and DX, respectively, as previously reported [8, 9]. f_u determines the fraction of the drug concentration that is not bound to plasma proteins and is thus available to enter cells and interact with GC receptors, i.e., the fraction of the concentration that is pharmacologically active