The period that a drug is in contact with a particular substrate in the oral cavity is substantivity. Drugs that have a prolonged duration of contact are considered to have high substantivity. In the oral cavity, substantivity depends on two important pharmacokinetic features: the degree of reversible nonspecific binding to oral reservoirs and the rate of clearance by salivary flow (Fig. 42.2).
Oral reservoirs are an important source for the continued release of drugs. The oral compartments that accumulate a drug must reversibly bind large portions of the administered dose and release therapeutic concentrations of free drug to the site of action over long periods. Therefore, effective agents with high substantivity ideally would not bind irreversibly, nor would they bind with high affinity to oral reservoirs.
Salivary flow also will significantly affect the sub-stantivity of topically applied liquid agents. The clearance of an agent from the oral cavity is directly proportional to the rate of salivary flow. Hence, during periods of high salivary flow, a greater release of drug from oral reservoirs is necessary to maintain therapeutic concentrations. Strategies that use natural or drug-induced periods of low salivary flow can increase the substantivity of an oral agent.
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