Pharmacokinetic properties, influence

Ensuring an adequate depth of anesthesia depends on achieving a therapeutic concentration of the anesthetic in the CNS. The rate at which an effective brain concentration is achieved (ie, time to induction of general anesthesia) depends on multiple pharmacokinetic factors that influence the brain uptake and tissue distribution of the anesthetic agent. The pharmacokinetic properties of the intravenous anesthetics (Table 25-1) and the physicochemical properties of the inhaled agents (Table 25-2) directly influence the pharmacodynamic effects of these drugs. These factors also influence the rate of recovery when the administration of anesthetic is discontinued. 

Peptidomimetics have found wide application as biostable, bioavailable, and often potent surrogates of naturally occurring peptides. They form the basis of important families of enzyme inhibitors and they act as receptor agonists and antagonists. Peptide chemists are also gaining a deeper understanding of the structural features of this class of compounds that influence their ability to permeate biological membranes and their pharmacokinetic properties. 

Several hundred semisynthetic derivatives have been prepared in an effort to obtain substances with better biological activities (for references see Ref.s)). Particularly positions 3 and 4 of the naphthoquinone ring system (numbering system as proposed by Prelog7 8) have been extensively substituted, since it has been shown that structural changes in these two positions do not critically affect the action of the substance on the target enzyme, the bacterial RNA polymerase (cf. Chapter 3.). They can, however, influence other parameters such as its ability to penetrate into cells, its pharmacokinetic properties and resorption, which are all important for clinical use as an antibiotic. Rifampicin (U.S. rifampin), which is a widely used orally active tuberculostatic agent, is a 3-(4-methyl piperazinyl)-iminomethyl derivative of rifamycin SV, synthesized via the 3-formyl derivative (Fig. 5)10 ... 

We wished to discover which pharmacokinetic property is of special importance for nitrothiazole in vivo action. In a separate experiment it was shown that particle size had no decisive influence on in vivo activity. Increasing experimental evidence indicates that absorption and distribu-... 

It is generally accepted that glycosides are more water-soluble than the respective aglycons. Attaching the glycosidic moiety to a molecule increases its hydrophilicity. This effect influences pharmacokinetic properties of the respective compounds, e. g., circulation, elimination and concentration in the body fluids. 

Other M blockers differ mainly in their pharmacokinetic properties, which can influence their Jinical uses. 

Advances in genetic engineering methods have enabled the generation of a variety of different antibody fragments and fusion proteins, and allowed the construction of molecules, the properties of which are tailored for the specific requirements of the intended therapeutic application [30]. These properties focus on efficacy -that is, the biological activity that addresses the mechanism of action. In addition, issues such as biochemical and biophysical stability, solubility, and production yield which influence the cost of goods (COG), and the pharmacokinetic properties as well as the immunogenicity of the protein, play an important role (see Table 1.1). 

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