Plasma protein binding, free drug principle

For more about plasma protein binding and the free drug principle, see Trainor, G.L. The importance of plasma protein binding in drug discovery. Expert Opin. Drug Discovery 2007, 2, 51-64, and Trainor,... 

Plasma Protein Binding and the Free Drug Principle Recent Developments and Applications... 

A similar strategy was employed to identify a DPP-IV inhibitor (6) with good in vivo potency in a mouse model of diabetes [44], Plasma protein binding, as assessed by shift assay (50% serum), was presented for all final compounds. The compound selected as having the best overall profile was active in vivo at 0.1 mg/kg. The activity at 1 h post-dose was consistent with the free drug principle - total plasma concentration 269 nM murine-free fraction 4% unbound plasma concentration 11 nM in vitro potency versus murine DPP-IV 6nM. 

G.L. Plasma Protein Binding and the Free Drug Principle Recent Developments and Applications , Chapter 31 in Annual Reports in Medicinal Chemistry, Volume 42, Macor, J.E., Ed. (San Diego, Academic Press, 2007). 

These are also die major frictors involved in acquired resistance to cisplatin (7,8). Hie genoal phaimacokinetic principle is diat free unbound drug is the active principle, allowing distribution to tissue. Thus an important parameter in general is tissue availability - stability in plasma and protein binding may be manipulated by qiprtqiriate formuladon and liposomes and other mediods of formulation have n used (3). 

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