Time of maximum concentration

Most researchers have found pseudo-first-order behavior for the various steps, and so it is possible to match theoretical curves with data to obtain the best rate constant values. Unfortunately, in most instances, too few data points were obtained to generate a unique theoretical fit. It is absolutely imperative that data be obtained for at least four conversion levels that are well spaced in the conversion matrix and extend to over 95% conversion. The partially hydrogenated dibenzothiophene intermediates are most often never detected as their desulfurization rates are extremely high (fcD, and kn2). The cyclohexylbenzenes and bicyclohexyls can arise from two different routes, and the concentrations of their precursors (biphenyl and cyclohexyl-biphenyl, respectively) pass through maximum values that can easily be calculated from the relative values of the formation and conversion rate constants. However, unique values for these relative rates can only be predicted if data are available well prior to and well beyond the times of maximum concentrations for these intermediates, because minor experimental errors can confuse curve-fitting optimization. 

Tmax, time of maximum concentration AUC, area under the curve. 

The mechanism of absorption after SC or IM administration is thought to occur via the lymphatic system. The mAbs enter the lymphatic system by convective flow of interstitial fluid into the porous lymphatic vessels. The molecular mass cut-off of these pores is >100-fold the molecular mass of mAbs. From the lymphatic vessels, the mAbs are transported unidirectionally into the venous system. As the flow rate of the lymphatic system is relatively low, mAbs are absorbed over a long time period after administration. The resulting time of maximum concentration (tmax) is much later (typically 1-8 days), and the systemically available fraction (F) is equal or lower (typically 0.5-1.0) compared to the IV administration of mAbs. For example, SC injection of 40 mg adalimumab results in a tmax of approximately 5 days, and F is approximately 64%. 

Tmax The time of maximum concentration or time of maximum exposure. 

Assay performance criteria for biopharmaceuticals are often highly variable therefore strict statistical criteria that attempt to rigorously establish traditional in vivo bioequivalence may not always be appropriate. In some cases an assessment of rate and extent of absorption as indicated by the maximum concentration (Cmax), time of maximum concentration (Tmax) and area under the curve (AUC) may be needed. In other cases complicating factors related to binding proteins, endogenous concentration, and unusual concentration-time profiles may need to be considered [15]. In cases where complications may arise from immune response to heterologous proteins, cross-over designs are inappropriate. 

As with all previous models, the effects of different model parameters on the plasma concentration versus time relationship can be demonstrated by mathematical analysis of the previous equations, or by graphical representation of a change in one or more of the variables. The plasma concentration (Cp) is proportional to the absorbed dose (FD) and inversely proportional to the compartment 1 distribution volume (Vj). Thus an increase in FD or a decrease in Vj both yield an equivalent increase in Cp, as illustrated in Figure 10.81. Note that the general shape of the curve, including the time of maximum concentration and slope of the distribution phase and the terminal line, is not a function of FD or Fi. The hybrid elimination rate constant X2) and the elimination half-life 3.re inversely... 

After injection of the sample onto the column the compounds that do not interact with the stationary phase will be eluted at time in the void volume Vq. The void volume represents the sum of the interstitial volume between the particles of the stationary phase and the accessible volume within the particle pores. The retention time of the sample (t,) is the time from injection to the time of maximum concentration in the eluted peak. The retention volume is the volume of solvent required to elute the solute as measured from the... 

Maximum Plasma Concentration (C Time of Maximum Concentration (T ax)... 

Time of maximum concentration (Tmax) is the time required to reach Cmax- As with Cmax, Tmax is usually determined from direct observation of the plasma concentration-time profile. The unit of Tmax is time (e.g., hour). 

The curves of Figure 2.9 exhibit the complex structure of the surface film. With increasing depth there is a peak of iron in the oxidized state at approximately 0.3 nm, and a peak of chromium in the oxidized state at about 1 nm irrespective of immersion time. The maximum concentration of oxidized iron decreases and the maximum concentration of oxidized chromium increases with increasing immersion time. 

The oceanic distribution of cobalt is similar to that of manganese, although cobalt concentrations are 10-100 times smaller maximum concentrations are 100-300 pM in surface waters, decreasing to 10 pM at depths below 1000 m. As concentrations of cobalt in seawater are so low, it may become biolimiting in open ocean surface waters. 

Figure 6-6 also shows the variation in the partial pressure of carbon dioxide in equilibrium with the lagoon s waters. The average value of this pressure exceeds the atmospheric value, 1, so on average, carbon dioxide is evaporating from the lagoon. The evaporation rate is greatest at times of maximum alkalinity and bicarbonate concentration and minimum carbonate ion concentration. 

The Time for Maximum Concentration, 7max, is the third important component of bioavailability studies. It is a measure of the rate of drug absorption. A lower 7max represents a faster absorption and a higher Tmax represents a slower absorption. Similar to Cmax, the 7max is read directly from the plasma concentration versus time profile. The 7max in Figure 12.2 is 6 hours. 

The concentration of the reactant A decreases regularly with time while that of intermediate B increases, passes through a maximum and then finally decreases to zero. The value of maximum concentration will depend on the rate of its formation and rate of its disappearance. The formation of final product C will start after formation of a certain amount of intermediate. Therefore, the final product will be formed with a certain induction period. 

Somewhat surprisingly, microdialysis has also revealed that the time to maximum concentration (T ax) within the CNS is close to the Tj ax value in blood or plasma, irrespective of lipophilicity. For example, the CNS Tj ax for atenolol (log D7 4 = - 1.8) occurs at 2 min in the rat after intravenous administration [8]. In addition the rate of elimination (half-life) of atenolol and other polar agents from the CNS is similar to that in plasma or blood. The implication of these data is that poorly permeable drugs do not take longer to reach equilibrium with CNS tissue than more lipophilic agents... 

It should be noted that pharmacokinetic data are included, which places a strain on the bioanalysts and laboratory facilities. However, with proper planning and adequate development time, preliminary but reasonably reliable data can usually be obtained within 2 or 3 days of receiving samples. Knowledge of maximum concentrations, dose proportionality of AUC and half-lives of the parent molecule and major metabolites greatly adds to making rational decisions about adverse events, times for sampling and measurements, the appropriate next dosage increment and the interval that should be allowed between study occasions. 

Drug/Food interactions The time to maximum concentration of zonisamide is delayed in the presence of food, but no effect on bioavailability occurs. 

FIGURE 4.2 A Effect of differences in elimination rate ion the maximum concentration (C, J and time to maximum concentration (F ax) reached after a single oral dose. The drug absorption rate is the same (Ka = 1 h ) for curves A and B. The for curve A is 6 hours the P for curve B is 2 hours. B Differences between absorption rates can have a pronounced effect on the time (T ax) which the maximum concentration (C ,x) reached. Curve A shows an orally administered drug with an absorption rate 4 times faster than that of curve B. Curve C shows the effect of a 50% decrease in bioavailability of drug A. The half-life (4 hours) is similar for scenarios A-C. 

Tests on gninea pigs have shown that a 5 percent by volume concentration of ethylene oxide vapor kills in a short time. The maximum concentration for 60 minutes without serious disturbance was 0.3 percent by volume. 

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