Pharmacokinetic administration, distribution factors

Furthermore, pharmacokinetic administration, distribution, metabolism and excretion (ADME) factors affect drug bioavailability, efficacy and safety, and, thus, are a vital consideration in the selection process of oral drug candidates in development pipelines. Since solubility, permeability, and the fraction of dose absorbed are fundamental BCS parameters that affect ADME, these BCS parameters should prove useful in drug discovery and development. In particular, the classification can used to make the development process more efficient.For example, in the case of a drug placed in BCS Class II where dissolution is the rate-limiting step to absorption, formulation principles such as polymorph selection, salt selection, complex formation, and particle size reduction (i.e., nanoparticles) could be applied earlier in development to improve bioavailability. 

Mechanism of Action A direct thrombin inhibitor that reversibly binds to thrombin-active sites. Inhibits thrombin-catalyzed or thrombin-induced reactions, including fibrin formation, activation of coagulant factors V, VIII, and XIII also inhibits protein C formation, and platelet aggregation. Therapeutic Effect Produces anticoagulation. Pharmacokinetics Following IV administration, distributed primarily in extracellular fluid. Protein binding 54%. Metabolized in the liver. Primarily excreted in the feces, presumably through biliary secretion. Half-life 39-51 min. 

One of the factors that can alter the response to drugs is the concurrent administration of other drugs. There are several mechanisms by which drugs may interact, but most can be categorized as pharmacokinetic (absorption, distribution, metabolism, excretion), pharmacodynamic (additive or antagonistic effects), or combined interactions. The general principles of pharmacokinetics are discussed in Chapters 3 and 4 the general principles of pharmacodynamics in Chapter... 

Setting aside issues of compliance and administration errors, the therapeutic response experienced by each patient may be influenced by variations in pharmacokinetics (rate and extent of absorption, distribution, elimination) and pharmacodynamics (physiologic, pathologic, and genetic factors receptor interactions and tolerance). 

In contrast to penetrating radiation, which passes through tissue in a weU-known manner, or even with the more complex situations arising fiom nonuniform distributions of internally deposited radionuclides, dosimetry of chemicals is far more difficult. Factors requiring consider ation in chemical dosimetry include the type of chemical under consideration, dose, duration of exposure, route of administration, aU possible metabolic pathways, capacity of the chemical to affect its own metabolism, pharmacokinetics, rate of excretion, and dose to the biological target at sites of tumor formation (which may vary depending on the route of administration). 

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. 

Pharmacokinetics is the study of how the body affects an administered drug. It measures the kinetic relationships between the absorption, distribution, metabolism, and excretion of a drug. To be a safe and effective drug product, the drug must reach the desired si te of therapentic activity and exist there for the desired time period in the concentration needed to achieve the desired effect. Too little of the drug at such sites yields no positive effect (MTC) leads to toxicity. For intravenous administration there is no absorption factor. Total body elimination includes both metabolic processing and excretion. 

The optimal administration of drugs in clinical practice is facilitated by effective application of the principles of clinical pharmacokinetics (PK) and pharmacodynamics (PD). Relationships between drug levels in the systemic circulation and various body compartments (e.g., tissues and biophase) following drug administration depend on factors governing drug absorption, distribution, elimination, and excretion (ADME). Collectively, the study of the factors that govern the ADME processes is termed pharmacokinetics. 

Clearance. This usually refers to the total plasm clearance (or total whole blood clearance) afte infravenous administration. In some instances the total clearance afrer an oral dose has been included if the drug is known to be well absorbed and is no subject to significant first-pass metabohsm. Numerous factors and intersubject variations ma affect the absorption, distribution, metabohsm, and excretion of drugs. These include age, sex, and disease states such as renal impairment In additior results of analyses may be subject to imavoidable analytical inaccuracies. Consequently, friere may beconsiderable variations in the observed drug concentrations and in values for pharmacokinetic... 

Dose-response is dependent upon the actual amount of the compound that reaches the intended target site after administration. The term pharmacokinetics refers to the factors that influence this amount. There are four basic pharmacokinetic measures absorption, distribution, metabolism, and... 

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