Pharmacologically active drugs

The general definition of the bioavailability (F) of a drug following oral administration is the rate at, and extent to which, a pharmacologically active drug reaches the systemic circulation. The bioavaiiabiiity (F) of a compound is a consequence of several processes shown in Eq. (1) ... 

Table 2. Selected examples of mammalian vs. microbial metabolism of pharmacologically active drugs... 

Any drug known to be largely excreted by the kidney that has a body half-life of less than 2 hours is probably eliminated, at least in part, by tubular secretion. Some drugs can be secreted and have long half-lives, however, because of extensive passive reabsorption in distal segments of the nephron (see Passive Diffusion, earlier in the chapter). Several pharmacologically active drugs, both anions and cations, known to be secreted are listed in Table 4.5. 

Fluid-State PC. This PC is extracted from soybean, and its molecule contains mainly unsaturated fatty acids. Its transition temperature is approximately 0°C, and it is referred to as the fluid-state PC. The PC molecule has structure-forming properties, and is therefore used as an excipient, both in drugs and in cosmetic preparations. In addition, it is used as an pharmacologically active drug substance in oral, systemic, and topical formulations. 

In neonates drugs such as various penicillins, pheno-barbital, phenytoin, and theophylline have lower protein-binding affinity than in adults. This may increase the concentration of free or pharmacological active drug in neonates, and may also change the apparent volume of distribution. Thus, neonates may require different doses on a mg/kg basis compared to that for adults for these drugs to achieve appropriate therapeutic serum concentrations. 

Inconclusive evidence suggests that salicylic acid can potentiate valproate toxicity (mechanism unclear). Sulfafurazole, sulfamethoxypyridazine, possibly other sulfonamides, and sulfinpyrazone displace phenytoin from plasma protein binding sites with different affinities total phenytoin concentrations may underestimate the concentration of unbound (pharmacologically active) drug. 

D. E. Drayer, Pharmacologically active drug metabolites therapeutic and toxic activities, plasma and urine data in man, accumulation in renal failnre, in Handbook of Clinical Pharmacokinetics M. Gibaldi and L. Prescott (Eds.). ADIS Health Science Press, Sydney, 1983, pp. 114-132. 

The lignans are an interesting group of natural products than can serve as a reference in the search for pharmacologically active drugs in different therapeutical groups. In addition, they have phytoestrogen properties which justify their interest in dietetic. 

The formulation of pharmacologically active drug molecules in DDS can improve or abolish these unfavorable properties. However, there are also drawbacks in DDS development, such as system complexity, unwanted biologic effects, stability, costs of development and scale-up, as well as intellectual property issues. In the limited format of this review, it is not possible to cover all methods and references in the field. Hence, we concentrate this review on DDS for the delivery of peptides, DNA, plasmids, oligodeoxynucleotides, siRNA, and lipophilic nucleoside derivatives. Vaccine delivery systems will also be mentioned, and examples will be provided to demonstrate the general development trends. 

Bertelli A, Bertelli AA, Gozzini A, Giovannini L. Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs Exp Clin Res 1998 24 133-138. 

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