Systemic clearance intravenous infusion

Lability can be used to advantage to create drugs that are designed for topical or intravenous infusion administration. For topical administration compounds may benefit from rapid systemic clearance to overcome possible side-effects. Thus the compound is stable at its topical site of action (skin, eye etc.) but rapidly degraded by the esterases present in blood, liver and kidneys to its inactive metabolites. This approach renders the compound selective. 

Equation 9.98 permits one to calculate the infusion rate necessary to attain and then maintain the desired steady-state plasma concentration of a drug if the systemic clearance of the drug is available. Equation 9.98 also provides a convenient way to determine the apparent volume of distribution of a drug by means of intravenous infusion experiment if the infusion rate (Q), the elimination rate constant (K), and the steady-state plasma concentration (C )gg are known. 

The clearance of P-D-2-acetamido-2-deoxyglucosidase from the circulatory system and the clearance induced by modified glycoproteins have been studied in rats. Intravenous infusion of a purified P-D-2-acetamido-2-deoxyglucosidase from rat epididymis showed that the enzyme is cleared comparatively slowly. Kinetic and competitive experiments with P-D-2-acetamido-2-deoxyglucosidase and P-D-glucuronidase indicated that the lysosomal compartment of rat liver has an important role in clearing the enzymes. ... 

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