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Effect of bioavailability on Dose-Response relationships

  • Author Footnotes
    1 From the Departments of Pharmacology and Nutrition,Harvard University, Boston, Massachusetts.
    Peter Goldman
    Correspondence
    Requests for reprints should be addressed to Dr. Peter Goldman, Food and Drug Laboratory, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115.
    Footnotes
    1 From the Departments of Pharmacology and Nutrition,Harvard University, Boston, Massachusetts.
    Affiliations
    Boston, Massachusetts, USA
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  • Author Footnotes
    1 From the Departments of Pharmacology and Nutrition,Harvard University, Boston, Massachusetts.
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      To achieve the goals of drug therapy one must not only select theappropriate drug but also ensure that it is administered in the proper dose. Sufficient drug should be administered to achieve a therapeutic effect, yet not so much as to produce unwanted side effects. One desirable effect of hydrochlorothiazide, for example, is the control of hypertension. An undesirable effect is excessive potassium loss. The dosage range that is likely to cause the hypotensive effect without the potassium loss has been called the “therapeutic window”. In principle, hydrochlorothiazide can be combined with a potassium-sparing diuretic, such as triamterene, to lower blood pressure with a decreased risk of hypokalemia, and thus to “widen” the therapeutic window. The term “dose”, however, requires further description. Because of compliance problems we know that the patient does not necessarily adhere to the prescribed dosage schedule. Furthermore, because of the bioavailability of the pharmaceutical formulation, the dose the patient “takes” may not be the one that he or she actually gets. The formulation of the drug product determines how rapidly and completely the active ingredient of the drug dissolves in the gastrointestinal tract and subsequently gets absorbed into the bloodstream. Thus, the time course of the drug concentration in serum has become the measure of dose that is most directly related to dose-response relationships. Incompletely absorbed drug products are said to be poorly bioavailable. Such products are undesirable, not only because the patient receives a dosage that is on the average less than that expected, but also because poor bioavailability may lead to a great variation in dose. Thus, poorly bioavailable drug formulations increase the variability in dose-response relationships among patients and as a result jeopardize the attainment of therapeutic objectives.
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