Mechanisms that produce loss. Storage and elimination

4 Mechanisms that produce loss. Storage and elimination 

Ribonucleic acid combines with flat, well-ionized cationic drug molecules. Thus the principal storage of mepacrine 6.10) after intravenous injection is in the nuclei of capillaries where this anti-malarial does no harm and is available for replenishing the blood level (Hecht, 1936). Chondroitin, acid glycoprotein, and other anionic biopolymers 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. 

The ratio (r) of the number of molecules of drug bound to each molecule of protein is given by the equation  

Often it is more convenient to work with the dissociation constant (Ad) which is /K. This varies from 900 for sulfadiazine, which is poorly bound, to 11 for sulfadimethoxine ( Madribon , see Section 9.3), which is almost too well bound to be a useful drug. Unless more than 90% of a drug is bound by albumin, the renal clearance is not slowed, and the serum protein acts as a depot and not a site of loss. 

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