Absorption first-order

Apparent first-order absorption rate constant (min 1) ... 

It is far more difficult to establish the mechanism(s) of drug absorption in humans. Most investigators analyze drug absorption data in humans (from blood or urine data) by assuming first-order absorption kinetics. For the most part this assumption seems quite... 

Fig. 8 Influence of concentration on the rate of absorption from the in situ rat intestine. The linear dependence of absorption rate on concentration suggests an apparent first-order absorption process over the range studied. Absorption rates have been calculated from the data in Ref. 15 and the straight lines are from linear regression of the data. Key (O) erythritol ( ) urea ( ) malonamide.

Db = drug in the body De = eliminated drug ka = first-order absorption rate constant kei = overall elimination rate constant... 

Input functions [i.e., I(t)], describing the rate at which the administered dose enters a compartment, may have various forms depending on the administration schedule. The input function /(f) is added to the appropriate mass balance equation and can describe any drug administration pattern. First-order absorption... 

The first-order absorption rate constant introduced above may be directly related to the effective permeability coefficient (Peff) using... 

The maximum absorbable dose (MAD) can be derived from the mixing tank model as shown by Johnson and Swindell [29], The amount of drug absorbed (Xa) at any time is a function of a first-order absorption constant (Ka) and the amount of dissolved drug (Xd) as described in Eq. 6. 

C(t) modeled according to two-compartment model with zero-order and first-order absorption Pharmacokinetic/pharmacodynamic relationship modeled using Hill model with first-order absorption. Modeled parameters matched experimental parameters when bicompartmental model with zero-order input was used. Linear PKs, anticlockwise hysteresis loop established for all doses studied. Apomorphine and growth hormone concentration predicted with good accuracy... 

The time evolution of plasma drug concentration can be treated by a simple model that assumes first-order absorption and first-order elimination of the drug. If [Dq] is the effective concentration of the drug dose, appearance of drug in the plasma will obey the relationship ... 

As shown above, the plasma drug concentration usually exhibits a biphasic rise and fall that are characteristic of all two-step series first-order processes. When k is zero, there will only be first-order absorption without any elimination, and when k > k, drug absorption will be virtually instantaneous, followed by first-order elimination. 

A two-compartment open linear model has been described for the pharmacokinetic profile of cocaine after intravenous administration.14 The distribution phase after cocaine administration is rapid and the elimination half-life estimated as 31 to 82 min.14 Cone9 fitted data to a two-compartment model with bolus input and first-order elimination for the intravenous and smoked routes. For the intranasal route, data were fitted to a two-compartment model with first-order absorption and first-order elimination. The average elimination half-life (tx 2 3) was 244 min after intravenous administration, 272 min after smoked administration, and 299 min after intranasal administration. 

First-order absorption model with or without lag time... 

First-order absorption (with and without lag time) treated as a mixture model... 

Maximum concentration, time to maximum concentration, and first-order absorption rate constant Cp max, fmax, ka... 

Pegfilgrastim plasma concentrations were modeled using a two-compartment model with a delayed, first-order absorption process. The clearance of pegfilgrastim was described by parallel linear and neutrophil-mediated clearance pathways ... 

The changes in a drug s plasma concentration with time may be calculated for a specific pharmacokinetic model by substituting of the appropriate rate expressions into Equation (8.29). For example, for a one compartment model in which the drug exhibits first order absorption and elimination (Figure 8.10), it is possible to show that ... 

Expressions similar to Equation (8.30) may be obtained for drugs that do not exhibit first order absorption and elimination characteristics by substituting the appropriate kinetic relationships in Equation (8.29). For example, for a drug that exhibits zero order absorption and first order elimination kinetics, Equation (8.29) becomes ... 

For absorbable substances, a first-order absorption term can be coupled with the convection-dispersion (6.15) to model both the fluid flow and the absorption process ... 

The absorption of freely soluble drugs having various values of k a was studied. Initially, the relationship between the simulated k a values and the corresponding conventional ka values, which are computed from the simulation assuming first-order absorption, was explored. An amount of instantly dissolved mass of q0 = 20, 000 was inserted in the input end of the tube and both profiles of the fraction of the mass that was absorbed and exited the tube were recorded. To find out the relationship between k a and ka, the following exponential equation was used to fit the simulated data of the fraction of dose absorbed Fa vs. time ... 

Figure 6.21 Phase plane plot for a drug obeying one-compartment model disposition with first-order absorption and elimination. Time indexes each point along the curve. The time flow is indicated by the arrows, while the. x-axis intercept corresponds to cmax-...

In contrast to highly lipophilic compounds, hydrophilic toxicants characterized by higher water solubility, e.g. hydrogen chloride and fluorine, are primarily adsorbed by the wet mucosa membranes of the throat and trachea in the upper respiratory tract. This is also the primary area for G-agent first-order absorption according to higher water... 

FIGURE 4.10 Model representing the absorption of a drug dose (Mq) from a gut compartment to a plasma compartment. The first-order absorption constant a determines the rate at which drug remaining in the gut (M) is transferred to plasma (X). 

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