Distribution Drug Transport

Blood is drawn as whole blood, that is, cells and plasma. Drug concentrations are measured in plasma, not whole blood. Whole blood is spun down in a centrifuge to allow separation of plasma from the cellular components. Plasma is more homogeneous than whole blood and therefore easier to analyze. The blood-to-plasma ratio of most drugs falls in a range of 0.5-1.5, and a value of 1 is generally not an unsafe assumption. In other words, the concentration of a drug in whole blood is often assumed to be the same as that 

FIGURE 3.16 Plasma protein binding for selected drugs  

---

The same assumptions apply to CoMFA as to ordinary Hansch analysis. These are additivity of effects and the availability of structurally similar (congeneric) molecules. The method does not account for pharmacokinetic effects, such as distribution, elimination, transport and metabolization. A prospective drug may appear to bind well to the receptor or enzyme, but may not reach the target site due to undesirable pharmacokinetic properties [8]. 

Seydel, J. K. Coats, E. A. Cordes, H. P. Weise, M., Drug membrane interactions and the importance for drug transport, distribution, accumulation, efficacy and resistance, Arch. Pharm. (Weinheim) 327, 601-610 (1994). 

RK Jain, J Wei. Dynamics of drug transport in solid tumors Distributed parameter models. J Bioeng 1 313-330, 1977. 

Kusuhara, H. and Y. Sugiyama. Role of transporters in the tissue-selective distribution and elimination of drugs transporters in the liver, small intestine, brain and kidney. J. Control. Release 2002, 78, 43-54. 

Lipophilicity is an important property of molecules in relation to their biological activities. It is one of the key physiochemical parameters that determine the distribution and transport of drugs into the body and target organs. Measurements of lipophilicity, expressed as the logarithm of the... 

K., Steiner, I Baumgartner, C. and Muller, M. (2005) Influence of functional haplotypes in the drug transporter gene ABCB1 on central nervous system drug distribution in humans. Clinical Pharmacology and Therapeutics, 78, 182-190. 

Interpretations of activity differences between a pair of agonists in terms of events at the receptor usually rest upon the assumption that drug transport factors play only a secondary role. Although this might seem reasonable in the case of a- and /3-prodine in view of their isomeric nature, preliminary results indicate that their potency differences may be related primarily to differences in their ease of penetration of the C.N.S. (in rats brain levels of /3-prodine exceed those of the a-isomer) [280]. If these findings be substantiated, conformational differences may then be related chiefly to processes governing the transport and distribution of the diastereoisomeric pair rather than to drug-receptor associations. 

---