Initial burst

Figures 2 and 3 illustrate the constant release of pilocarpiae over the seven day treatment period. An initial burst of dmg iato the eye is seen ia the first few hours. This is temporary and the system drops to the rated value ia approximately six hours. The total amount of dmg released ia this transitory period is less than that normally given ia pilocarpiae ophthalmic solutions. The ocular hypotensive effect of these devices is hiUy developed within 2 hours of placement ia the conjunctival sac, and the hypotensive response is maintained throughout the therapy. This system replaces the need for eyedrops apphed four times per day to control iatraocular pressure.

Studies of the pharmacokinetics of this deHvery system in two animal models have been reported in the Hterature. After iajection of these microspheres at three doses, leuproHde concentrations were sustained for over four weeks foUowing an initial burst (116). The results iadicated that linear pharmacokinetic profiles in absorption, distribution, metaboHsm, and excretion were achieved at doses of 3 to 15 mg/kg using the dmg loaded microspheres in once-a-month repeated injections. 

Working on challenging assignments early has the advantage of allowing you to identify and overcome problems early in the project, and to harness the initial burst of energy and attention that such projects typically receive. 

The rat has been previously used as a model animal for in vivo study of naltrexone (72). As shown in Figures 10 and 11, after an initial burst, the naltrexone plasma levels were 1.03 0.52 ng/mL/mg injected conjugate for P(HPG/LEU)-naltrexone-14-acetate and 0.70 0.39 ng/mL/mg injected conjugate for P(HPG/LEU)-naltrexone-3-acetate for 30 days. From these in vivo data, to achieve a similar plasma level in human, a subcutaneous injection dose of 100 to 500 mg can be predicted assuming that the volume of distribution of naltrexone per kilogram of body weight is of the same magnitude for both rats and humans. 

An initial burst effect was observed in all in vivo studies. There are several possible factors which may cause a burst effect physically absorbed free drug, surface effects, and local tissue inflammation during the initial period of injection. It has been shown that inflammation decreases local tissue pH (15,16) and causes release of hydrolytic enzymes which would increase the hydrolysis of labile bonds, thereby increasing the release of the drug and, subsequently, increasing plasma levels of drug. 

The in vitro degradation profiles of several TDI poly(phosphoester-ure thanes) are shown in Figure 2. It is not possible from this study to correlate the decomposition kinetics with the chemical structure, except for the fact that biodegradability is demonstrated. The in vitro release of 5-FU from PPU-7 is shown in Figure 3. After an initial burst, a reasonably steady and sustained release followed. The UV spectrum of the released 5-FU was identical to that of pure 5-FU, suggesting the chemical integrity of the drug. 

The kinetic expressions in Eqs. (134) and (136) take into account the initial burst of drug into the receiver and the possibility of cell-associated drug within a slow kinetic pool which is determined at t = °°. 

For well soluble compounds like the important co-factor NAD, the release was rather fast (within 1 hour) and to slow it we increased the viscosity inside the tubules, using as solvent water with 5 wt% of PVP (polyvinylpyrrolidone). In Figure 14.7 one can see 7 hours linear NAD release from halloysite [6]. An initial burst of 20 % in the release curve is typical for release from halloysite. 

Since L /M — 1 (in cgs units), it follows from a comparison of equations (7.18) and (7.19) that, for exponential decay in bolometric luminosity, v-1 7 Gyr. Thus a single strong initial burst seems to be ruled out as a dominant contributor in the solar neighbourhood. 

Properties of the 1-zone model were systematically studied by Talbot and Arnett (1971), who contrasted the instantaneous recycling approximation with an initial burst approximation which is the opposite extreme. In the latter case, most of the... 

Serine peptidases can hydrolyze both esters and amides, but there are marked differences in the kinetics of hydrolysis of the two types of substrates as monitored in vitro. Thus, the hydrolysis of 4-nitrophenyl acetate by a-chy-motrypsin occurs in two distinct phases [7] [22-24]. When large amounts of enzyme are used, there is an initial rapid burst in the production of 4-nitro-phenol, followed by its formation at a much slower steady-state rate (Fig. 3.7). It was shown that the initial burst of 4-nitrophenol corresponds to the formation of the acyl-enzyme complex (acylation step). The slower steady-state production of 4-nitrophenol corresponds to the hydrolysis of the acetyl-enzyme complex, regenerating the free enzyme. This second step, called deacylation, is much slower than the first, so that it determines the overall rate of ester hydrolysis. The rate of the deacylation step in ester hydrolysis is pH-dependent and can be slowed to such an extent that, at low pH, the acyl-enzyme complex can be isolated. 

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