Instantaneous absorption

Juwekar and Sharma [1] described the kinetics of the above reactions. The formation of calcium carbonate is non elementary reaction which involves the number of elementary steps as shown in Scheme 7.2, steps (iv) and (v) assumed to be instantaneous. Absorption of C02 gas and dissolution of Ca(OH)2 affects the nucleation step, both are considered as rate controlling steps. 

The equation is an approximation, adapted from that for intravenous dosing [81], corrected by addition of a term for absorption. Essentially it assumes instantaneous absorption of the dose, but for compounds with reasonable physico-chemical and PK properties that are expected to be suitable for once-a-day dosing, this approximation makes little difference to the predicted value of Cmin ss. Use of the relationship can provide a simple approach for estimating the required dose in man for a compound in the discovery phase. 

The function Cs represents the concentration tune course that would result from the instantaneous absorption of a unit amount of drug and can be estimated from either i.v. bolus data, oral solution, suspension or rapidly releasing (in vivo) immediate release dosage forms. 

Instantaneous absorption rate Qx - molar gas flow rate Vg - superficial gas velocity... 

The major advantage of the microporous coatings is the speed with which they absorb inks as a result of their porosity. This instantaneous absorption provides, in effect, instant drying. Additional characteristics of the microporous layer are the high water fastness and its compatibility with both dye and pigment inks. 

The extensive lipophilicity of DMM allows the substance to pass readily through biological membranes. This chemical property facilitates its near instantaneous absorption by the skin, lungs, and gastrointestinal tract, and results in its accumulation in depots of adipose tissue, plasma proteins, and brain. Approximately 10% of the body burden of organic mercury is localized in the brain. 

Instantaneous Absorption) Model 221 Bolus IV (Instantaneous Absorption)... 

Bolus rV (Instantaneous Absorption) 10.11.4 Estimating Model Parameters from... 

Other drug delivery situations that do not closely mimic true instantaneous absorption can still be approximated by this absorption model, as long as the absorption process occurs much more quickly than all other processes. For example, an orally ingested drug for which absorption is essentially complete after one or two hours could be approximated as instantaneous absorption if the distribution, metabolism, and excretion processes all take several days to approach completion. Note that even if an extravascular drug delivery can be treated as instantaneous absorption, the bioavailability F) can still range from 0 to 100%. Specific criteria for when the instantaneous absorption approximation can be used will be provided later in... 

Figure 10.10 Graphical representation of an approximately instantaneous absorption rate.

One-Compartment Bolus IV Injection (Instantaneous Absorption) Model... 

ONE COMPARTMENT BOLUS IV INJECTION (INSTANTANEOUS ABSORPTION) MODEL... 

The one-compartment bolus IV injection model is mathematically the simplest of aU PK models. Drug is delivered directly into the systemic circulation by a rapid injection over a very short period of time. Thus the bolus rV injection offers a near perfect example of an instantaneous absorption process. Representation of the body as a single compartment implies that the distribution process is essentially instantaneous as well. The exact meaning of the assumptions inherent in this model are described in the next section. Model equations are then introduced that allow the prediction of plasma concentrations for drugs with known PK parameters, or the estimation of PK parameters from measured plasma concentrations. Situations in which the one-compartment instantaneous absorption model can be used to reasonably approximate other types of drug delivery are described later in Section 10.7.5. 

The standard one-compartment bolus IV (or instantaneous absorption) model makes three inherent assumptions about the ADME processes that occur after drug delivery. The specific nature and implications of each of these assumptions are described in this section. 

As in all instantaneous absorption models, the entire absorbed dose of drug is taken to enter the systemic circulation instandy at time zero (< = 0). This provides an excellent approximation of the rapid drug delivery direcdy into the systemic circulation provided by a bolus IV injection, which truly occurs over a very short period of time (typically several seconds). However, this assumption does not actually require a strict interpretation of the word instantaneous. Even if an absorption process takes a substantial period of time (minutes or hours), it can still be approximated as instantaneous as long as absorption occurs quickly relative to other ADME processes. Thus, other routes of drug delivery besides a bolus IV injection can be approximated by instantaneous absorption if the time it takes for the absorption process to be essentially complete is very small compared to the half-life of elimination. The equations throughout most of this section are written specifically for a bolus IV injection, but modifications that can be employed to apply the equations to other drug delivery methods are described in Section 10.7.5. 

Itwas previously discussed in Section 10.7.5.1 that under certain circumstances, a zero-order drug delivery process of short duration can be approximated as an instantaneous absorption process. The conditions under which this approximation gives reasonable results can be investigated mathematically using model simulations. These simulations are made by keeping the total absorbed dose FD = F- ko- T) the same in each simulation. As illustrated in Figure 10.39, the instantaneous absorption model provides a reasonable approximation when T < This criteria can be employed as a... 

Figure 10.39 Graphical illustration of how closely a one-compartment instantaneous absorption model approximates one-compartment zero-order absorption plasma concentrations for different values of T relative to...

Three special cases are considered for the one-compartment first-order absorption model. Eirst is a relatively rare situation known as a flip-flop situation. Second is the use of the one-compartment first-order absorption model to approximate the plasma concentrations of drugs that follow two-compartment kinetics. The last case considered is the identification of conditions when first-order drug delivery with rapid absorption can be modeled as an instantaneous absorption process. 

This assumption is the same for all instantaneous absorption models. See Section 10.7.1.1 for the details regarding this assumption. 

Estimation of two-compartment bolus IV (instantaneous absorption) parameters from measured plasma samples ends up being quite similar to the one-compartment first-order absorption case. Proper parameter evaluation ideally requires at least three to five plasma samples be collected during the distribution phase, and five to seven samples be collected during the elimination phase. As in the one-compartment first-order absorption case, two stages of linear... 

These then represent all the parameters that have been introduced so far for the two-compartment bolus IV (instantaneous absorption) model. Several additional parameters will be introduced in the following sections. 

There are several common special case situations in which the two-compartment bolus IV model can be applied as a reasonable approximation for administration routes other than bolus IV injection. The means by which the two-compartment bolus IV model can be employed in these situations is described in this section. The criteria under which a drug following two-compartment instantaneous absorption can be approximated by a one-compartment instantaneous absorption model are also provided. 

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