Maximal concentration

A feature of Equation 10.6 is the fact that there are conditions where the binding will not diminish to basal levels in the presence of maximal concentrations of allosteric modulator. This effect is exacerbated by high levels of initial stimulation (as [A]/Ka oo). The maximal inhibition by an allosteric modulator for Equation 10.6 is... 

On average, 500 mOsm of waste products must be excreted in the urine per day. The minimum volume of water in which these solutes can be dissolved is determined by the ability of the kidney to produce a maximally concentrated urine of 1200 mOsm/1 ... 

PDPH is soluble in 0.1 M sodium acetate, pH 5.5, at a maximal concentration of 14.2 mg/ml. The reagent is particularly stable in acetonitrile for preparation of concentrated stock solutions. 

McCarron We do our best to have maximal concentrations of both InsP3 and caffeine. We apply lOmM caffeine from a puffer pipette. The cell receives a very high caffeine concentration, which is presumably saturating almost instantaneously. For the L1SP3 response we have set up our conditions to mimic the size of the transients that we get from caffeine. It is a maximal response that we are getting, at least as far as we can see from discharge from the store. 

Taylor The experimental observation from which this comes is as follows. First, we pretreat the permeabilized cells in our superfusion apparatus with 100 /rM Ca2+ for about a second, to drive the cells to the state where they can no longer respond to InsP3 (even at heroic concentrations). Next, we wash out the Ca2+ to a low cytosolic level of 200 nM. Then we look for how long it takes for the normal response to a maximal concentration of InsP3 to recover. That takes a long time. 

Compound Typical (or Maximal) Concentration Reported, ppm Reference... 

Therapeutic group Compound Maximal concentration detected (ng/L) References... 

The conclusions indicated above were also reached from computer analysis of the rather more arbitrary model of Penniston et al (14) by Dearden and Townend (15). In view of the large variations with P of time to maximal concentration, they expressed concern at the widespread practice... 

Absorption/Distribution - Following oral administration, telithromycin reached maximal concentration at about 1 hour. 

An interesting example concerns the enhancement of absorption of orally active thrombin inhibitors taking into account that oral absorption can be increased by lowering the basicity of the functions of the Pi substituent, a fluorine atom has been introduced in ortho position of the amidrazone function. This has led to an enhancement of the peak of blood maximal concentration after oral administration of the compound in a rat (Fig. 8) [46]. 

The pharmacokinetics of topiramate are linear with peak plasma concentrations (occurring in about 2 hours) of 25 pM after 400 mg daily (Shank et al., 2000). Topiramate is poorly bound to plasma proteins (15%) and it binds to erythrocytes. In rats the maximal concentration in the brain when administered at 10 mg/kg was 10 pM (Shank et ah, 2000). It is not extensively metabolized in humans and is eliminated (70%) unchanged in urine. Six minor metabolites have been identified, none with anticonvulsant activity. The average elimination half-life is 21 hours (Shank et ah, 2000). 

Figure 5.2 Plasma concentration curve of drug after single and repeated administration Csj. nax, maximal steady-state plasma concentration after repeated administration Css av, average steady-state concentration after repeated administration Css mm- minimal steady-state concentration after repeated administration n. maximal plasma concentration after single oral dose t Inax. time to maximal concentration after single oral dose t plasma half-life after single oral dose AUC, area under the concentration vs. time curve...

There are several reasons for different routes of administration used in clinical medicine (Table 3-3)—for convenience (eg, oral), to maximize concentration at the site of action and minimize it elsewhere (eg, topical), to prolong the duration of drug absorption (eg, transdermal), or to avoid the first-pass effect. 

Similarly, drugs injected into the SC or IM space are separated from the blood compartment by the endothelial cells of the capillaries. From the interstitial space, such drug molecules must first diffuse toward and then partition into the endothelial cell membrane. After traversing these cells, the drugs must then partition on the luminal, or blood facing, side of these cells into the blood, which carries them away. By this dilution effect, the blood presents sink conditions, thus maintaining a maximal concentration gradient, dCm/dx, to drive diffusion toward the blood. 

The sarcoplasmic transport system can be fueled in addition to ATP by a great number of phosphate compounds which differ considerably in their chemical nature. Not only the natural nucleoside triphosphates126 but also para-nitrophenylphosphate,27 acetyl phosphate128 or carbarmyl phosphate129 can drive calcium transport. While there are considerable differences between the rates with which calcium transport proceeds with the different substrates, they are all used with the same coupling ratio of two and the pump can establish similar maximal concentration ratios (Fig. 7)... 

Table 8. Residual calcium levels and maximal concentration ratios accomplished by the sarcoplasmic reticulum calcium pump fueled with different substrates58,, 26 ...

If you define chemical breakthrough as the time it takes for the half-maximal concentrations to pass across the plastic membrane, will a 1 millimeter thick LLDPE sheet be effective at retaining benzene for 20 years ... 

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