Zero-order rates

Schmid s observation of the dependence of the reaction rate on the square of the concentration of nitrous acid was interpreted by Hammett (1940, p. 294) as due to the rate-limiting formation of dinitrogen trioxide, N203. The consequent attack of the amine by N203 was postulated to be faster therefore the concentration of the amine has no influence on the overall rate (zero order with respect to amine). Similarly, Hammett regards the second factor of Schmid s equation for diazotization in the presence of hydrochloric or hydrobromic acid as the result of the formation of nitrosyl halide. 

A constant rate (zero-order kinetic behaviour) maintained during all, or the greater part of the process may be accounted for [487] by the following reaction models, illustrated in Fig. 5. These alternatives may be distinguished by microscopic observations. 

The rate equation describes the variation in response variable R (with initial value of Rq) the measure response appears at a constant rate (zero order) of and is eliminafed by the first-order constant. The indirect response models will generally fall info fwo caf-egories inhibition or stimulation function. The inhibition response is classically described in ferms of IC q, fhe drug concenfration fhaf produce 50% of maximal inhibition (e.g., action of S5mfhefic glucocorticoid on adrenal glands or effecf of furosemide on sodium absorption in fhe loop of Henley) and is a number from 0 fo 1 where 1 represents total inhibition ... 

The rate of ethanol degradation in the liver is limited by alcohol dehydrogenase activity. The amount of NAD" available is the limiting factor. As the maximum degradation rate is already reached at low concentrations of ethanol, the ethanol level therefore declines at a constant rate (zero-order kinetics). The calorific value of ethanol is 29.4 kj g Alcoholic drinks—particularly in alcoholics—can therefore represent a substantial proportion of dietary energy intake. 

In other indications such as hypertension, the OROS technology (oral osmotic system developed by ALZA) has already proven its value, and therefore it seemed appropriate to use this technology with its typical, virtually constant, release rate (zero-order kinetics) for once-daily opioid tablets. Such a morphine tablet is already available, but is not yet on the market, and a hydromorphone OROS is currently being clinically developed by Knoll. 

Under certain conditions, such as in organic media, the formation of the NOj ion [Eqs. (10.6) and (10.7)] becomes rate-determining, resulting in a rate zero order in the aromatic ... 

In the case of controlled drug-delivery systems, the goal is to have the drug released at a relatively constant rate (zero-order kinetics) at a concentration within the therapeutic range. It is obviously important to minimize the amount of time the concentration is in... 

Mass (mg) First-Order Rate Zero-Order Rate... 

The reaction rate remains constant up to high conversion rates (zero order in relation to benzene). Two side reactions must be avoided because they lower the cyclohexane purity. These are conversion to methylcydopentane and hydrocracking. The isomerization equilibrium of cyclohexane to methyicyclopentane corresponds to a conversion of 68 per cent at 200°C, reaching 83 per cent at 300°C. This makes it necessary to select a catalyst that does not favor this reaction. With nickel-based systems, the reaction appears only above 250°C. Moreover, the hydrogen must not contain impurities liable to poison the active phases introduced. 

Figure 2 (a) Bulk erosion of biodegradable controlled-release polymer implants leads to unpredictable release profiles, (b) Polymers exhibiting surface erosion release drug at nearly constant rate (zero-order kinetics) as they dissolve in water. (From Ref. 61.)... 

Figure 10.2 Administration of drug at a constant rate (zero-order process) by an intravenous infusion.

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