Volume of distribution and tissue level errors in instantaneous intravenous input assumptions

A comparison was made between instantaneous input assumption and short-term zero-order infusion for 1 and 2 min for several drugs showing fast distribution to the tissue compartments. The errors ranged from 9 to 40% for the volume of the central compartment, from 0.7 to 11% for the volume of distribution following pseudo-distribution equilibrium, and from 11 to 34% for the volume of distribution change at the end of the 2-min infusion period. Significant errors in the tissue levels also were observed. It was suggested that all intravenous administrations be considered as short-term zero-order inputs.