Dose-effect curve, pharmacodynamics

Drug Dose 67 Routes of Administration Drug Absorption 72 Drug Distribution 74 Drug Elimination 75 Pharmacodynamics 80 The Dose-Effect Curve Effective and Lethal Doses Drug Interactions 86 Summary 89... 

Pharmacodynamics is a discipline within the broader topic of pharmacology, which focuses on how a drug brings about a particular response, and the effective levels that are required in order to elicit such a response. Some of these basic data will have emerged from the research-based activities that initiate the development of most drugs today. However, considerable additional studies are required to establish detailed dose-response curves so that the optimum therapeutic level can be chosen. 

Figure 3 Rodent pharmacodynamic effects versus CbjU for 6. Dashed lines represent a twofold separation from the in vitro functional assay EC50 (122 nM, dashed arrow). mSLA, mouse spontaneous locomotor activity mPPI, mouse prepulse inhibition DRC, dose-response curve SD, single dose. (See Color Plate 4.3 in the Color Plate Section.)...

Pharmacodynamic studies deal more specifically with how the drug brings about its characteristic effects. Emphasis in such studies is often placed upon how a drug interacts with a cell/organ type, the effects and side effects it induces, and observed dose-response curves. 

The range of doses and plasma concentrations that exhibited pharmacodynamic effects in animals, the nature of the effects, and the slope of the dose-response curve... 

To date there has been relatively little work correlating the pattern of deposition with the therapentic outcome or pharmacodynamic effects (118,124, 133-135). This perhaps is not too surprising, as most p-agonists are administered at or close to supramaximal doses and therefore generally administered close to the plateau of the dose response curve, while the therapeutic effects of inhaled steroids are observed over weeks and indeed for bronchial hypersre-sponsiveness further benefits are still being observed after a couple of years of therapy. 

To assess the potential for an interaction between raloxifene and warfarin, 15 healthy postmenopausal women each received single doses of warfarin 20 mg before and during 2 weeks of dosing with raloxifene 120 mg/day (37). Raloxifene reduced the oral clearance of R- and A -war-farin respectively by 7.1 and 14% and the oral volume of distribution by 7.4 and 9.8%. Raloxifene reduced the maximum prothrombin time by 10% and the area under the prothrombin versus time curve from 0-120 hours by an average of 8%. The authors concluded that raloxifene may produce a small increase in systemic warfarin exposure but a reduced pharmacodynamic effect. Since the effects are slight this interaction is unlikely to have clinical consequences. 

Figure 9 Pharmacodynamic relationship observed at steady state in 24 subjects for various doses of a sustained-release (once daily) verapamil formulation. The concentration measure used is the area under the S-verapamil concentration over the 24-hr dosing interval the effect measure used is the area under the PR interval curve (measured with Holter monitor) over the 24-hr dosing interval. The doses of sustained-release verapamil that resulted in each concentration-effect pair are also shown.

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