Error dependent on renal function when monoexponential equation assumed

The recent paper by MacKichan and coworkers, which appeared in the November, 1977, issue of the J ournal , states that there is an important error dependent on renal function when a one‐compartment model is used to calculate drug clearance values from data better fitted to a more complex model. This error is related to the magnitude of the ratios of the exponents and constants of the two‐compartment model and is independent of the pathway of elimination of the drug. Lidocaine, a drug with a rapid metabolism rate, shows an error when a one‐compartment model is used, but this error is independent of renal function. 4,5 Even for lidocaine, dosage recommendations calculated from a one‐compartment model are not significantly different from those calculated from a two‐compartment model. 4 Thus the general conclusion of MacKichan and coworkers that “the clinical importance of this error cannot be overlooked” requires qualification. MacKichan and co‐workers imply that a one‐compartment model is inappropriate for calculating clearance values for antipyrine, tolbutamide, and pentobarbital in man. The literature documents that there are very small differences in clearance values calculated for these drugs when the one‐compartment model is compared to the two‐compartment model. 1–3