Drug dose-response relationships

The law of mass action has been successfully applied to many drug dose-response relationships since the early work of Clark. The systematic relation between the dose of a drug and the magnitude of its response is based on three assumptions (1) response is proportional to the level of receptor occupancy (occupancy theory), (2) one drug molecule combines with one receptor site, and (3) a negligible fraction of total drug is combined with the receptors. These assumptions must also apply to Beidler s equation. 

Drugs—Dose-response relationship. 2. Drugs—Dosage. 3. Oral medication. 4. Drug development. I. Zheng, Jack. 

Logistic function generally yields a sigmoidally shaped line similar to that defined by drug dose-response relationships in biological systems. It is defined by y = (1 + e-(a + bx))-1. 

Thus, a drug may produce response either with low efficacy by occupying many receptors or with high efficacy by occupying few receptors. The issues of dealing with agonist—dose response relationships can be complex and reference should be made to detailed texts (44,45). 

Drug-receptor interactions Dose-response relationships Molecular modeLs of receptors and signal transduction mechanisms Biotr an s fo r m ati on Ph ar macokine t ios Ph armacody namics... 

Generally, in vivo nonclinical studies should be designed to include a sufficient number of animals per group to permit a valid estimation of a drug s toxicologic and pharmacologic effects in terms of incidence, severity and the dose-response relationships involved (Thomas and Myers, 1998). The latter point requires, as... 

Pharmaceuticals are intended to have human exposure. Furthermore, pharmaceuticals are intended to have biological effects on the people that receive them. Frequently, the interpretation of results and the formulation of decisions about the continued development and eventual use of a drug are based on an understanding of both the potential adverse effects of the agent and its likely benefits, as well as the dose separation between these two. This makes a clear understanding of dose-response relationship critical, so that the actual risk/benefit ratio can be identified. It... 

Ideal for studying the dose-response relationship for QT interval prolongation taking into account all the pharmacological properties of a compound The dog model is one of the most widely used anesthetized rabbits (especially female rabbits) have also been proposed for high sensitivity It provides complementary information with respect to in vitro tests (activity of metabolites, measurement of plasma drug concentrations, calculation of the volume of distribution) Possibility to induce experimental TdP... 

Another difference from drug therapy is that the dosing interval of a nutritional supplement is often not a critical parameter for a positive outcome. This lack of a strong dose-response relationship is an important consideration in setting of standards for dietary supplements and is in stark contrast to the situation for drug products. 

Lewis, S.C., Langman, M.J.S., Laporte, J.R., Matthews, J.N.S., Rawlins, M.D., and Wiholm, B.E., Dose-response relationships between individual nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and serious upper gastrointestinal bleeding a meta-analysis based on individual patient data, Br. ]. Clin. Pharmacol., 54, 320, 2002. 

There are severai pharmacokinetic parameters that are reievant to the ciinicai use of drugs. These heip quantify a dose-response relationship, or... 

Ginical testing starts with Phase I studies on healthy subjects and seeks to determine whether effects observed in animal experiments also occur in humans. Dose-response relationships are determined. In Phase n, potential drugs are first tested on selected patients for Ltillmann, Color Atlas of Pharmacology... 

An important qualification must be made. While a biomarker may be of proven value in establishing whether a drug has the desired effect in patients or healthy volunteers (see Section 4.6.3) and for evaluation of the dose-response relationship, a biomarker may not be a surrogate for the clinical endpoint. Thus, suppression of testosterone after an initial rise will give an almost immediate endpoint for the effect of GnRH analogues in prostate cancer but the relationship breaks down later in the disease. Measures of blood glucose control are vital... 

Of course, it is not always necessary to rely on biomarkers for rapid evaluation of dose-response relationships in ED. Thus, efficacy of new drugs is readily demonstrated in terms of the clinical endpoint for diseases, such as migraine, inflammatory pain, asthma, psoriasis, glaucoma and many others. 

Lewis SC, Langman MJ, Laporte J-R, Matthews JN, Rawlins MD, Wihohn BE. Dose-response relationships between individual nonsteroidal antiinflammatory drugs and serious upper gastrointestinal bleeding. Brit J Chn Pharm 2002 54 320-6. 

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