Zero-order absorption models

Example 4 Mixture of First-Order Absorption and Zero-Order Absorption Models... 

One-Compartment IV Infusion (Zero-Order Absorption) Model... 

ONE-COMPARTMENT IV INFUSION (ZERO-ORDER ABSORPTION) MODEL... 

Zero-order absorption occurs when drug enters the systemic circulation at a constant rate. An IV infusion, in which a drug solution is delivered directly into the systemic circulation at a steady flow rate, represents an idealized zero-order absorption case. Because of this, standard zero-order absorption models are typically called IV infusion models and are designed specifically for the IV infusion case. This particular section deals with the one-compartment IV infusion model, so as in the previous one-compartment bolus IV model, the body is modeled as a single compartment with the implication that the distribution process is essentially instantaneous. As with the other standard models, the exact meaning of the assumptions inherent in this model are described next. Model equations then are introduced that allow the prediction of plasma concentrations for drugs with known PK parameters, or the estimation of PK parameters from measured plasma concentrations. Modification of the one-compartment IV infusion (zero-order absorption) model to approximate other types of steady drug delivery are described in Section 10.8.5. 

The standard one-compartment IV infusion (or zero-order absorption) model makes three inherent assumptions about the ADME processes that occur during and after drug delivery ... 

Three special cases are considered for the one-compartment zero-order absorption model. First is the extension of the IV infusion equations to cover steady extravascular drug delivery. Second is the use of the one-compartment zero-order absorption model to approximate the plasma concentrations of drugs that follow two-compartment kinetics. The last case... 

This assumption is the same for aU zero-order absorption models. See Section 10.8.1.1 for the details regarding this assumption. 

The values of Bi, li, B, and from the terminal line analysis and the method of residuals analysis can then be used to evaluate all remaining model parameters. The micro rate constants for the IV infusion (zero-order absorption) model are given by the equations... 

This gives values for all two-compartment IV infusion (zero-order absorption) model parameters. 

The two-compartment zero-order absorption model is more complex and harder to work with than the one-compartment zero-order absorption model. Thus the one-compartment model is often used when it provides a reasonable approximation to the two-compartment values. In fact, the one-compartment model is often used even when a drug is known to significantly deviate from single compartment kinetics. Just as in the case of the two-compartment bolus IV injection model in Section 10.10.5.3, as a general rule of thumb the one-compartment model can be employed with reasonable accuracy as long as < 2 82- When this simplification is used, the one-compartment IV infusion equations in Section 10.8 can be used without modification for an IV infusion, or with the modifications listed in Section 10.11.5.1 for steady extravascular delivery. 

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