Rx Drug Develpment

Rx Drug Develpment - BME 210 Biomedical Computer Simulation...

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BME 210 Biomedical Computer Simulation Methods Therapeutic Drug Development I Introduction II. Compartment Models A. Examples of Compartment Transfer B. General Compartment Models C. Examples of Compartment Models III. Compartment Matrices IV. Least Squares Estimation – An Example V. Root of an Equation – One Unknown A. Newton’s Methods B. Secant Methods C. Application to Least Squares VI. MATLAB Implementation A. Newton’s Method B. Secant Methods VII. Least Squares Estimation – General Formulation VIII Solution to General Least Squares via Direct Function Minimization Study Problems Study Problem Solutions
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BME 210 Spring 2009 Therapeutic Drug Development 2 Therapeutic Drug Development I. Introduction For a clinician to successfully treat a patient's disease with a therapeutic drug requires, among other things, an understanding of the drug's pharmacokinetics and pharmacodynamics in the patient under treatment. Pharmacokinetics is the study of the absorption, distribution, biotransformation and excretion of drugs. It is these processes that determine, for a given dose of the drug, the concentration of the drug at its sites of action in the body. Pharmacodynamics is the study of the biochemical and physiological mechanisms of action of a drug in the body's tissues. Mathematical models have proven to be invaluable in understanding both the pharmacokinetics and pharmacodynamics of drugs, and as such, are routinely used in the evaluation of new drugs and as a tool for the safe and effective management of drug therapy. Figure 1 is a schematic diagram illustrating the subprocesses involved in understanding the pharmacokinetics of a drug. The figure shows the relationship between the absorption, distribution (to "tissue reservoirs"), binding (e.g., to plasma proteins), biotransformation (e.g., metabolism by liver), and excretion (e.g., in the urine) of the drug. Also shown is the movement of the drug from the circulation to its site of action. The latter includes both the therapeutic and toxic sites of action in the body. A major motivation for the development of mathematical models to describe the pharmaco- kinetics of drugs has been provided by the observation that drug effects (pharmacodynamics) are, in many cases, better predicted by the plasma concentration of the drug than by the actual amount (dose) of the drug given. In such cases, when both the therapeutic and toxic effects of the drug parallel its concentration in the blood, the administration of the drug is generally manipulated so as to achieve a specified target plasma drug concentration (or concentration profile) in the individual patient under study. Drug dosage individualization based on pharmacokinetic models is routinely performed for many acute care drugs in most large city hospitals as well as in many community hospitals. This has been brought about by the development of rapid, simple and reliable drug concentration measurement procedures (assays) and by the widespread availability of microcomputers and software to perform the necessary computations.
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This note was uploaded on 04/12/2009 for the course BME 210 taught by Professor D'argenio during the Spring '07 term at USC.

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Rx Drug Develpment - BME 210 Biomedical Computer Simulation...

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