Kinetics, monophasic

Recently, Brich and coworkers (40) reported the synthesis of lactide/glycolide polymers branched with different polyols. Polyvinyl-alcohol and dextran acetate were used to afford polymers exhibiting degradation profiles significantly different from that of linear poly-lactides. The biphasic release profile often observed with the linear polyesters was smoothened somewhat to a monophasic profile. Further, the overall degradation rate is accelerated. It was speculated that these polymers can potentially afford more uniform drug release kinetics. This potential has not yet been fully demonstrated. 

We shall first consider some straightforward kinetics, in which the loss of A, in the treatment referred to above, is monophasic and the reaction is unidirectional, that is, it leads to 95% loss of A. 

The beta phase clearance kinetics of human IgG and therapeutic antibodies is typically monophasic and abides to a log-linear relationship of serum concentration with time after administration. However, in rare cases we have found that certain administered mAbs are immunogenic to the mouse and elicit mouse-anti-human antibodies. In this case, there is a bi-phasic kinetic, typically appearing at days 5-6 after antibody administration and resulting in a precipitous antibody loss. This complication can be overcome by the use of immunodeficient hFcRn transgenic mice, described in Section 3.7. 

Plasma pantoprazole concentrations decline monophasically after oral administration, with a mean plasma terminal half-life (tj P) of 0.9 to 1.9. Despite the short i r of pantoprazole, inhibition of acid secretion, once accomplished, is long lasting, persisting after the drug has been cleared from the circulation. Thus, the plasma kinetics of pantoprazole have little bearing on its antisecretory action [1],... 

The kinetic information can be used as well to deduce if a compound is bound homogeneously or not. The kinetics of flutax and paclitaxel dissociation from (3-tublin are monophasic, which indicates a single rate limiting step, consistent with most of the compound bound to the same site. However, dissociation of Epothilone A from the binding site shows biphasic behaviour, which would be consistent with the compound distributed between the external and the luminal site, with a temperature-dependant equilibrium (Table 2) which favours the outer site at higher temperatures. 

The insolubility of enzymes in monophasic organic systems has a controlling influence on the kinetics of enzymatic catalysis in organic media. Insolubilized enzymes are subject to intraparticle and external diffusional limitations which can mask the true, intrinsic kinetics of catalysis. These limitations are particularly severe for highly active and purified enzymes such as horseradish peroxidase. One way to overcome this problem is to increase the surface area of the enzyme in contact with the organic solvent. 

When, under identical conditions, ascorbic acid was used instead of mercaptoethanol, the reaction gave products with 3°/2° carbon reactivity of 0.28-0.42, suggestive of an autoxidation process (12). Furthermore, the kinetics of the reaction are biphasic for 2-mercaptoethanol and monophasic for ascorbic acid. These kinetics are consistent with the generation of a new catalytic system by the coordination of the thiol to the ferric center(s). For either reductant, bleaching of the complex was observed within minutes in the absence of substrate. 

Viscose rayon is inherently a weak fibre, particularly when wet, therefore it is highly susceptible to damage if enzymatic hydrolysis is not controlled. The enzymatic hydrolysis of viscose fibres causes a decrease of the intrinsic viscosity from 250 to 140 ml/g and an increase in crystallinity from 29 to 39% after 44 h [34]. Strong changes of the structure, however, are not typical for the enzymatic hydrolysis of cellulosic materials. Neither cotton nor wood pulp show an essential decrease of the DP during enzymatic hydrolysis [35-37]. The kinetics of the enzymatic hydrolysis of regenerated cellulose fibres before and after acid prehydrolysis changes the kinetics from a monophasic to a biphasic first order reaction [38]. 

Figure 17 Time course of the kinetic experiment performed with surfactant substrate (19) in vesicular 20, Br upon addition of Cu(NO3)2 ([copper(II)] = 5 x 10 M, pH 5). The first part was run at 25 °C, i.e. above the of the membrane. At this temperature the kinetics are monophasic. The second part was run at 10 °C. If during the time at 25 °C copper(II) permeation occurred, monophasic kinetics would be expected since all the substrate (in the internal and external layers) is exposed to the metal ion. Since a biphasic process is observed, no permeation has occurred and the stay of the vesicles above f involves only flip-flop of (19)...

Fig. 8 (B) top is a plot of absorbance changes at 820 nm at various times after photoexcitation by the 500/ laser pulse. A computer fit of the data points yields a monophasic, exponential increase with a risetime of 3.0 0.6/75 for the [P680 O] -> [BbSO O"] reaction. The same kinetics are found over the entire 750-850 nm region.

Monitoring the removal of compounds from the epidermis is indicative of measuring the compound s dermal absorption. The disappearance of radiolabeled benzo[a]pyrene and its metabolites from the epidermis was monophasic, following first order kinetics with a half-life of approximately 2 hours (Melikian et al. 1987). Recovery of the radiolabel was 99-100% throughout the period of the experiment (8 hours), indicating that volatilization of benzo[a]pyrene from the skin was not a confounding factor (Melikian et al. 1987). In contrast, removal of one of its metabolites,... 

C-ABT-773 was metabolized by liver microsomes and hepatocytes from mouse, rat, dog, monkey, and human. The metabolic pathway was oxidation, and its profile was similar in all species to give A -desmethyl-ABT-773 (M-1) as the major metabolite (Fig. 11). The kinetics of ABT-773 metabolism were examined in four human liver microsomes over a drug concentration range of 1.5-50 pM. The metabolism of ABT-773 followed monophasic Michaelis-Menten kinetics with K = 22.3 xM and = 5.2 nmol/mg protein/min [108]. 

Using the methylviologen cation radical (MV +) formed by pulse radiolysis, monophasic kinetics of cytochrome reduction are observed with a rate constant of 4.5 X 108 M 1/s (1.1 X 108 M 1/s on a per heme basis) at pH 8.0 with the Hildenborough cytochrome (36). This very fast second-order process approaches the diffusion controlled limit. Moreover, the reverse reaction can be estimated to be 7.8 X 104 M-1/s, which suggests that the reaction takes place primarily with the highest potential heme (the A E 0 between heme I and MV + is 190 mV, consistent with an equilibrium constant of approximately 103). Interestingly, the kinetics with MV + are ionic strength dependent, which is consistent with a plus-plus interaction,... 

A final point involves a report of the kinetics of CO binding to human P450 2E1 following flash photolysis . The kinetics appeared to be monophasic and the rate was decreased in the presence of (400 mM) ethanol. One interpretation of the results is that binding of the substrate makes P450 2E1 more rigid. ... 

The time course of orientational changes induced by electric fields contains information on the orientation mechanism, and on the electrical and geometrical properties (main dipole axis, length) of the aligning and deorienting molecules. For instance, permanent dipole orientation of a given particle type in the presence of a constant electric field builds up with zero slope and has two modes, whereas the build-up of induced dipole orientation starts with maximum slope and is characterized by only one time constant. The deorientation relaxation of a system of identical particles, after termination of the step pulse, is monophasic, independently of the presence of permanent or induced dipoles. Table 3 summarizes the characteristic features of the rotational kinetics indicated by electric dichroism and birefringence for small perturbations. We see that there are a number of specific relationships to differentiate between permanent and induced dipole mechanism. In particular, the technique of field-reversal is a sensitive indicator for the relative contributions of permanent or induced dipoles. 

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