Formal theory of discrete drug dosing regimen adjustments

Summary

A formal theory of discrete drug dosing regimen adjustments has been developed, based on the recognition that in practical drug administration the possibilities for partition of a drug formulation are limited, and that only definite dosing intervals are acceptable in clinical practice. Normalization of the treatment regimen variables was used to reduce the innumerable cases of dosing regimens subject to adjustment to a limited number of categories. By replacing the dosing interval by the corresponding daily dosing frequency it was possible to associate with each treatment regimen a characteristic variable — the daily dose. The definition of the minimal normalized maintenance dose and the minimal normalized dosing frequency then permitted establishment for each case of a complete set of normalized dosing regimen adjustments, which consisted of all acceptable adjustments of both the variables of the regimen. This could be subdivided into several equivalency classes according to the value of the associated daily dose. The adjustment procedure of a dosing regimen can be regarded in general as a two stage process. In the first stage the normalized daily dose is selected according to the relative reduction in the total body clearance of the drug. This is followed, if necessary, by choice of which ever of the equivalent dosing regimens is more appropriate in the given situation. The theory also allows simultaneous change in both dosing regimen variables, thus enhancing the limited possibilities for adjustment. Its practical employment can be facilitated by use of a series of decision tables, although the formal character of the theory permits its implementation on mini- or desk-top computers.