Mechanisms of loss. Storage and elimination

Three principal mechanisms whereby an active substance can be lost before it reaches the effective receptor are storage, elimination, and chemical inactivation (Fig. 3.2). Veldstra referred to the loci where these processes 

Storage, Three important storage sites of loss are lipids (for neutral substances), ribonucleic acid (for cations), and albumin (for anions). Body-fat is such a lipid, and it stores drugs of high liposolubility, e.g. thiobarbiturates [such as thiopental ( Pentothal ) 3.4) ], and dibenamine. This appears to be a simple lipid/water partition effect (Brodie and Hogben, 

Plant-growth accelerators, such as a-naphthylacetic acid, are taken up by the fatty reserves of pea shoots these sites of loss can be blocked with a biologically inactive, but more liposoluble, analogue such as decahydro-naphthylacetic acid (Veldstra, 1956). 

Ribonucleic acid combines with the cations of highly basic substances. Thus the principal storage of mepacrine (6.9) after intravenous injection is in the nuclei of capillaries where this antimalarial does no harm and is available for replenishing the blood-level (Hecht, 1936). Chondroitin and other anionic biopolyers also store cations. 

Serum albumin, on the other hand, is a storage site for many drugs, most of which are weak acids. Table 3.3 shows how this affinity varies not only from species to species, but also among two series of chemically related substances. Man, who binds drugs by serum albumin more strongly than other mammals do, usually metabolizes drugs less readily than other mammals. 

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