The concept of retrometabolic drug design encompasses two distinct approaches.  One approach is the design of soft drugs (SDs), new, active therapeutic agents, often isosteric or isolelectronic analogs of a lead compound, with a chemical structure specifically designed to allow predictable metabolism into inactive metabolites after exerting their desired therapeutic effect(s).  The other approach is the design of chemical delivery systems (CDSs).  CDSs are biologically inert molecules intended to enhance drug delivery to a particular organ or site and requiring several conversion steps before releasing the active drug.
Although both retrometabolic design approaches involve chemical modifications of the molecular structure and both require enzymatic reactions to fulfill drug targeting, the principles of SD and CDS design are distinctly different.  While CDSs are inactive as administered and sequential enzymatic reactions provide the differential distribution and ultimately release the active drug, SDs are active as administered and are designed to be easily metabolized into inactive species.  Assuming an ideal situation, with a CDS the drug is present at the site and nowhere else in the body because enzymatic processes destroy the drug at those sites.  Whereas, CDSs are designed to achieve drug targeting at a selected organ or site, SDs are designed to afford a differential distribution that can be regarded as reverse targeting.