Dispositional interactions

For excretion processes, the same reasoning may be used as for absorption. Cases of interaction are only to be expected when active processes are involved. Increased excretion of a chemical following administration of an osmotic diuretic or alteration of the pH of the urine are well known examples of dispositional interaction. 

Dispositional interactions are those in which one chemical affects the disposition of the other, usually metabolism. Thus, one chemical may increase or inhibit the metabolism of another to change its toxicity. For example, 2,3-methylenedioxynaphthalene inhibits cytochrome P-450 and so markedly increases the toxicity of the insecticide carbaryl to flies (potentiation) (see chap. 5). Another example, which results in synergy, is the increased toxicity of the organophosphorus insecticide malathion (see chap. 5) when in combination with another organophosphorus insecticide, EPN. EPN blocks the detoxication of malathion. Many chemicals are either enzyme inhibitors or inducers and so can increase or decrease the toxicity of other chemicals either by synergism or potentiation (see chap. 5). 

The retarding influence of the product barrier in many solid—solid interactions is a rate-controlling factor that is not usually apparent in the decompositions of single solids. However, even where diffusion control operates, this is often in addition to, and in conjunction with, geometric factors (i.e. changes in reaction interfacial area with a) and kinetic equations based on contributions from both sources are discussed in Chap. 3, Sect. 3.3. As in the decompositions of single solids, reaction rate coefficients (and the shapes of a—time curves) for solid + solid reactions are sensitive to sizes, shapes and, here, also on the relative dispositions of the components of the reactant mixture. Inevitably as the number of different crystalline components present initially is increased, the number of variables requiring specification to define the reactant completely rises the parameters concerned are mentioned in Table 17. 

Two product barrier layers are formed and the continuation of reaction requires that A is transported across CB and C across AD, assuming that the (usually smaller) cations are the mobile species. The interface reactions involved and the mechanisms of ion migration are similar to those already described for other systems. (It is also possible that solid solutions will be formed.) As Welch [111] has pointed out, reaction between solids, however complex they may be, can (usually) be resolved into a series of interactions between two phases. In complicated processes an increased number of phases, interfaces, and migrant entities must be characterized and this requires an appropriate increase in the number of variables measured, with all the attendant difficulties and limitations. However, the careful selection of components of the reactant mixture (e.g. the use of a common ion) or the imaginative design of reactant disposition can sometimes result in a significant simplification of the problems of interpretation, as is seen in some of the examples cited below. 

Dickins M, van de Waterbeemd H, Simulation models for drug disposition and drug interaction. Drug Discov Today Biosilico 2004 2(l) 38-45... 

The SECSY spectrum of the coumarin presents cross-peaks for various coupled nuclei. These cross-peaks appear on diagonal lines that are parallel to one another. By reading the chemical shifts at such connected cross-peaks we arrive at the chemical shifts of the coupled nuclei. For instance, cross-peaks A and A exhibit connectivity between the vinylic C-4 and C-3 protons resonating at 8 7.8 and 6.2, respectively. The C-4 methine appears downfield due to its )3-disposition to the lactone carbonyl. Similarly, cross-peaks B and B show vicinal coupling between the C-5 and C-6 methine protons (8 7.6 and 7.1, respectively) of the aromatic moiety. The signals C and C represent the correlation between the oxygen-bearing C-11 (85.4) andC-12 (84.6) methine protons in the side chain. These interactions are presented around the structure. 

The microorganisms do not necessarily always form the same metabolites as humans in a similar manner, but they can be useful for studies of drug interactions, disposition, etc. [11]. Although there is no correlation between the mammahan and microbial isozymes, the mechanism involved in microorganisms is still unknown, but may be similar to that involved in animals. Additionally, the fungal metabohsm of the compounds is often affected by the concentration, nutritional factors, inducers, and environmental factors [12]. 

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