Pharmacokinetic drug - carrier conjugate

Rnally, pharmacokinetic and pharmacokinetic/pharmacodynamic modelling can be used for the purpose of prediction of the concentration-time profile of the drug and drug-carrier conjugate after repeated administration from single dose data, as well as for the prediction of the dose needed to maintain the concentration at the target site within a therapeutic window. 

Numerous experimental therapeutics have shown potency in vitro however, when they are tested in vivo, they often lack significant efficacy. This is often attributed to unfavorable pharmacokinetic properties and systemic toxicity, which limit the maximum tolerated dose. These limitations can be overcome by use of drug carriers. Two general types of carrier systems have been designed drug conjugation to macromolecular carriers, such as polymers and proteins and drug encapsulation in nanocarriers, such as liposomes, polymersomes and micelles. 

The overview of HPMA copolymer-anticancer drug conjugates and their antitumor activities can be found in Table 1. As with other carrier systems, attachment of an anticancer drug to the HPMA copolymer carrier changes the drug s pharmacokinetics. For example, ADR attached to HPMA copolymers via a Gly-Phe-Leu-Gly sequence showed a 15-times longer intravascular half-life and a 100-fold lower initial peak level in the heart tissue when compared to free... 

These studies have also demonstrated that the biological properties (e.g. epitope-related immunogenicity or drug-related antitumor effect) and pharmacokinetics (e.g. blood survival, tissue distribution) of conjugates are greatly influenced by the chemical structure of the carrier. ... 

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