PHAR 7632 Chapter 4

One Compartment IV Bolus

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Total Body Clearance (Cl)

Clearance is an important pharmacokinetic parameter that describes how quickly drugs are eliminated, metabolized or distributed throughout the body. It can be viewed as the proportionality constant relating the rate of these processes and drug concentration. For example the rate of elimination of a drug can be described by Equation 4.10.1.

Equation 4.10.1 Rate of Elimination versus Concentration

In Equation 4.10.1 the elimination rate constant, dX/dt, is related to the concentration of drug remaining. The proportionality constant for this relationship is Clearance, Cl. The symbol for clearance is Cl and the units are volume per time or ml/min, L/hr.

Equation 4.10.1 can be rearranged to give Equation 5.10.2 for clearance.

Equation 4.10.2 Clearance calculated from Rate and Concentration

Clearance can be calculated from this equation by measuring the amount of drug eliminated during some time interval and the drug concentration at the midpoint of this collection interval. The clearance of the endogenous material, creatinine, is measured by this method as described in Chapter 16 to provide a measure of renal function.

Clearance can also be calculated from the integral of Equation 4.10.2. Integrating dX/dt and Cp with respect to time give Dose and AUC, respectively. The total amount that can be eliminated is the total amount administered, that is, the dose. Thus, clearance can be calculated as:

Equation 4.10.3 Clearance calculated from Dose and AUC

In the case of the one compartment model with an IV bolus dose the rate of elimination can be expressed as:

thus a value for Total Body Clearance, CL, can be estimated from kel and V for the one compartment model.

Equation 4.10.4 Clearance calculated from kel and V

The clearance of a drug can be used to understand the processes involved in drug elimination, distribution and metabolism. Relating clearance to a patient renal or hepatic function can be used in the determination of suitable drug dosage regimens.

Figure 4.10.5 Clearance, V, kel and t_1/2

Click on the figure to view the Java Applet window

References

Clearance has been discussed on the PharmPK listserv.

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