Kinetic efficacy

Initial studies carried out in our laboratories served to confirm that the Eu(III) texaphyrin 8b is in fact capable of catalyzing the hydrolysis of phosphate diesters. For instance, using the ammonium salt of uridylyl-3, 5 -uridine (UpU) as a substrate, it was found that this particular texaphyrin is able to effect catalytic hydrolysis (as judged by a controlled HPLC product analysis) with a pseudo-zero order rate of (9.1 1.6) x lO mMh By comparison, under identical conditions, Eu(N03)3, was found to effect UpU hydrolysis with a pseudo-zero order rate of (2.7 0.2) X lO mMhwhile Morrow s Eu(III) hexaamine Schiff base complex ("EuHAM"),27e one of the better alternative systems known, induced hydrolysis with a corresponding rate of (4.1 0.4) x lO mMh- Additionally, these same studies served to confirm that the Eu(III) texaphyrin complex 8b is far more stable in solution than the corresponding HAM-derived product. Thus, from both a kinetic efficacy and intrinsic stability perspective, the Eu(III) texaphyrins appear to be the best metal-based systems for use in antisense applications. 

Such arguments are based on the assumption that the nitronium ion is the nitrating agent in all of the media under consideration as regards nitration with acetyl nitrate, they certainly do not prove the efficacy of the nitronium ion unless the participation of the latter can be shown to be also consistent with the kinetic evidence. 

Kinetics of Pesticide Biodegradation. Rates of pesticide biodegradation are important because they dictate the potential for carryover between growing seasons, contamination of surface and groundwaters, bio accumulation in macrobiota, and losses of efficacy. Pesticides are typically considered to be biodegraded via first-order kinetics, where the rate is proportional to the concentration. Figure 2 shows a typical first-order dissipation curve. 

Many factors affect the mechanisms and kinetics of sorption and transport processes. For instance, differences in the chemical stmcture and properties, ie, ionizahility, solubiUty in water, vapor pressure, and polarity, between pesticides affect their behavior in the environment through effects on sorption and transport processes. Differences in soil properties, ie, pH and percentage of organic carbon and clay contents, and soil conditions, ie, moisture content and landscape position climatic conditions, ie, temperature, precipitation, and radiation and cultural practices, ie, crop and tillage, can all modify the behavior of the pesticide in soils. Persistence of a pesticide in soil is a consequence of a complex interaction of processes. Because the persistence of a pesticide can govern its availabiUty and efficacy for pest control, as weU as its potential for adverse environmental impacts, knowledge of the basic processes is necessary if the benefits of the pesticide ate to be maximized. 

Real-time spectroscopic methods can be used to measure the binding, dissociation, and internalization of fluorescent ligands with cell-surface receptors on cells and membranes. The time resolution available in these methods is sufficient to permit a detailed analysis of complex processes involved in cell activation, particularly receptor-G protein dynamics. A description of the kinetics and thermodynamics of these processes will contribute to our understanding of the basis of stimulus potency and efficacy. 

Platt EJ, Dumin IP, Rabat D (2005) Kinetic factors control efficiencies of cell entry, efficacies of entry inhibitors, and mechanisms of adaptation of human immunodeficiency virus, J Virol 79 4347 356... 

Experience profound compositional shifts in use May experience phases changes in use Site in the disease s location Operate at variable drug activity Highly nonstationary state kinetics Application technique and amount are highly individualized Applications short-acting Local tissue levels tied to efficacy Used on diseased, damaged skin No easy bioequivalency endpoint Systemic absorption absolutely undesirable, but some unavoidable... 

Li+ required for efficacy by increasing its bioavailability and possibly to reduce some of the unpleasant side effects sometimes experienced with this drug. The toxicity of such ionophores and kinetics of ion complexa-tion, both association and dissociation, are obviously important factors under consideration in this field of research. 

The efficacy of penicillin-type antibiotics is constrained by the ability of bacteria to induce enzymes for their destruction. In relation to this problem, Page and coworkers (Buckwell et al., 1988a,b) have studied the hydrolysis of acylated penicillins [55] and cephalosporins [56] catalysed by a bacterial /3-lactamase (Tables A6.9 and A6.10). It is noteworthy that the two series of substrates show quite different responses to changes in the length of the acyl side chain (C2 to C12). For the penicillins, which are cleaved much more efficiently, there is a broad maximum in the kinetic parameters around C5 to C7, whereas for the cephalosporins there is a linear increase in kc/KM and... 

A paclitaxel fullerene derivative has been obtained by covalent linkage of the dmg to the C60 by means of an ester, the hydrolysis of which presents a favorable kinetic profile, with consequent release of paclitaxel (Zakharian et al., 2005). The in vitro tests show a good anticancer activity, holding out hope for enhancing the dmg efficacy... 

Okada and coworkers [66] discovered that the crystallization of this molecule from methanol yielded optically active crystals that were sometimes dextrorotatory and sometimes levorotatory, and that underwent rapid racemization upon redissol-ving in methanol. They went on to study the kinetics of this process as well as the nature of the different crystalline forms. [67, 69] Bonner [50, 65, 70] has extended and confirmed these observations and conclusions, with special attention to the possibility that the crystallization might provide the means for studying the efficacy of... 

As bioanalysis plays a key role during drug discovery and toxico-kinetic/pharmacokinetic evaluation of drug candidates, several improvements have been made in minimizing the time spent in performing bioanalysis and for the evaluation of drug efficacy. 

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