Pharmacokinetics of protease inhibitors and other drugs

A bifunctional compound comprising a protease inhibitor moiety, a linker, and a pharmacokinetic modulating moiety, wherein the linker is attached to the protease inhibitor moiety and the pharmacokinetic modulating moiety, and the pharmacokinetic modulating moiety gives the bifunctional compound a different pharmacokinetic behavior from that of the protease inhibitor moiety in the absence of the linker and pharmacokinetic modulating moiety, wherein the molecular weight of the bifunctional compound is less than about 5000 daltons and the molecular weight of the pharmacokinetic modulating moiety is less than about 1100 daltons.

In a method of administering a drug to a host in need of said drug, the improvement comprising:

• administering to said host an effective amount of a bifunctional compound comprising said drug or a derivative, fragment or analog thereof linked to a ligand for a presenter protein endogenous to said host, wherein said drug binds to a drug target and said ligand binds to a presenter protein that is not said drug target, wherein the bifunctional compound is administered in a controlled release formulation that operates according to a controlled release mechanism in addition to whatever controlled release is provided by the ligand.

A method for modulating at least one pharmacokinetic property of a drug upon administration to a host, the method comprising:

• administering to the host an effective amount of a bifunctional compound of less than about 5000 daltons comprising the drug or an active fragment, analog, or derivative thereof and a pharmacokinetic modulating moiety, wherein the pharmacokinetic modulating moiety binds to at least one intracellular protein and wherein the bifunctional compound modulates at least one pharmacokinetic property and one efficacy property upon administration to the host as compared to a free drug control.