Pharmacodynamics efficacy

Racine-Poon, A., Botta, L., Chang, T., Davis, F., Gygax, D., Liou, R., Ro-hane, P., Staehelin, T., VanSteijn, A., and Frank, W., Efficacy, pharmacodynamics, and pharmacokinetics of CGP 51901, an anti-immunoglobulin E chimeric monoclonal antibody, in patients with seasonal allergic rhinitis, Clinical Pharmacology and Therapeutics, Vol. 62, No. 6, 1997, pp. 675-690. 

Nab assays determine the potential to neutralize in vivo. However, these in vitro assay systems are static systems that do not take into consideration the dynamic interactions that occur in vivo (e.g., clearance of ADA-dmg immune complexes, equilibrium/affinity between drug/antibody/target). There are examples of Nab (even to endogenous protein) that have no/minimal impact on drug efficacy, pharmacodynamics, or adverse events [24,25], Thus, one shouldkeep in mind that whenNab assays are used, the results must be evaluated in the context of other clinical end points to determine their significance. 

Very recently, ( )-trani-2-[3-methoxy-4-(4-chlorophenylthioethoxy)-5-(A-methyl-Al-hydroxyureidyl)methylphenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (229), a tetrahydrofuran derivative has been identified as a dual inhibitor for its activity as a PAF receptor antagonist and as a 5-LO enzyme inhibitor (Scheme 30.40). Armed with the advantage of concomitant inhibition, compound 229 offered many therapeutic advantages in terms of efficacy, pharmacodynamics, and cost for the treatment of such skin disorders. 

The therapeutic efficacy of a dmg is generally measured in terms of ED q or ID q which represent the concentration of dmg which produces 50% of the maximum effect or 50% of maximum inhibition. LD q represents the concentration of dmg that produces 50% fataUties in test animals. The therapeutic index is the ratio of the ED q versus LD q. Detailed descriptions of the terminology and fundamental principles of pharmacology are available (32) (see Pharmacodynamics). 

It is one of the peculiarities of herbal drugs that their indications have for the most part been determijied empirically. The reason is easily understood most herbal drugs have been used for a very long time to alleviate or cure illnesses and more especially disorders. Their introduction in therapeutics happened at a time when pharmacodynamics and pharmacokinetics were unknown concepts, when there was no Medicines Act to require proof of the quality, efficacy, and innocuity of herbal medicines. Today, when introducing a new medicine, extensive investigations are required in the interest of safety. To many the requirement of the proof of activity of such a drug as chamomile appears to be superfluous, but nevertheless, as a representative of a scientifically oriented pharma-... 

Although in many cases an enantiopure drug can be safer than the racemate, the advantages are clear. The final formulation of the drug product could be reduced inhalf, potential side effects could be minimized, and the resulting pharmokinetic and pharmacodynamic studies could clearly determine the efficacy of the active pharmaceutical ingredient (API) [21]. 

The overall objective of clinical trials is to establish a drug therapy that is safe and effective in humans, to the extent that the risk-benefit relationship is acceptable. The ICH process has developed an internationally accepted definition of a clinical trial as Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy. ... 

Samples of blood and excreta are taken for laboratory analysis. It is expected that, at the end of this phase, you will have a preliminary estimate of the maximum dose that may be safely tolerated in humans, and also a basic profile of the drug s pharmacokinetic behaviour. Depending on the availability of appropriate analytical indicators, pharmacodynamic and indicative efficacy data may also be generated. The data acquired must be carefully analysed and assessed so that, based on the findings, appropriate Phase II trials can be planned. 

Purpose Explore Therapeutic Efficacy (dose ranging and dose-response curves, pharmacodynamics,... 

The consequence of moving consciously toward this model will be the provision of a robust and scalable IT infrastructure and systems able to cope with exponentially growing data mountains that will need to be integrated and shared, accessed and mined in the most effective way. It will also require formidable computing power and sophisticated algorithms to be able to simulate both organs and whole body systems to reduce expensive failures in the clinic and predict much earlier the pharmacokinetic and pharmacodynamic properties and toxicological and efficacy profiles of molecules in pharmaceu-... 

Assess appropriate selection of these medications for pharmacokinetic and pharmacodynamic DDIs (Table 52-6), need (e.g., do renal transplant recipients need to continue to take erythropoietin ), and efficacy. 

Even though there are important pharmacodynamic and pharmacokinetic differences among the various /1-blockers, there is no difference in clinical antihypertensive efficacy. 

Integration of both pharmacokinetic and pharmacodynamic properties of an agent is important when choosing antimicrobial therapy to ensure efficacy and prevent resistance. Antibiotics may demonstrate concentration-dependent (aminoglycosides and fluoroquinolones) or time-depen-dent (/l-1 acta ms) bactericidal effects. 

As a general rule, in vivo assays are more challenging than in vitro assays because the matrices for the samples are more complex. The most common use for in vivo assays is to measure the concentration of NCE dosed into a laboratory animal by collecting multiple sample time points, one can use the analytical results to plot the PK profile of the NCE and also obtain various PK parameters that help determine a test compound s PK properties. Preclinical PK parameters of a test compound are then used to predict its human PK parameters. Another use of in vivo assays is combining the results with pharmacodynamic (PD) observations to perform PK/PD modeling.77 82 PK/PD modeling is an important aspect of new drug discovery because it can be used to predict the exposures and durations required to determine clinical efficacy of a NCE. 

Coukell, AJ. and Faulds, D. 1997. Epirubicin An updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of breast cancer. Drugs. 53 453. 

The current case history will focus on the discovery of tegaserod and will summarize the pharmacodynamic effects in the GI tract and its therapeutic efficacy in IBS-C and CC. 

It has become increasingly accepted that the pharmacokinetic behavior of new drugs represents an important attribute, along with efficacy and safety. The frequency with which a drug must be taken is a function of several factors the half-life, the span between minimally efficacious concentrations and concentrations that cause side-effects, and the pharmacokinetic-pharmacodynamic relationship. Typically medicinal chemists optimize the predicted pharmacokinetics of... 

As it is often very difficult to quantify therapeutic performance with pharmacodynamic and clinical studies, pharmacokinetic studies are usually the most suitable tool to describe the performance of the drug product in vivo. Once a relationship between the plasma concentration of the drug or active moiety and the therapeutic effect has been established, BA may be considered to be the perfect surrogate parameter for efficacy and/or safety of a drug product. 

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