Figure 1. Theoretical changes, after a bolus dose, in the concentration of a muscle relaxant in plasma (solid lines) and in the biophase (broken lines) in time. (A) The concentration of a drug in plasma decreases as a result of clearance of the drug from plasma (curve A). The concentration in the biophase increases because of transfer of the drug from plasma to the biophase. When the concentrations in plasma and biophase are similar (arrow A), the maximum concentration in the biophase is reached and the peak effect is obtained. Thus the moment of equilibration between plasma and biophase determines the onset time. If the same drug is administered in the same dose but with a reduced clearance (curve B), the moment of equilibration would be later (arrow B) and at a higher maximum concentration in the biophase. Consequently, the onset time would increase and the peak effect would be larger. (B) In the case of a reduced plasma clearance (curve B), the dose must be reduced to obtain a peak effect similar to that induced by the drug with a normal plasma clearance (curve A). The time to maximum concentration in the biophase is not affected by the dose.