Systemic drug absorption

Adherence to the following guidelines can reduce systemic drug absorption and reduce the risk of adverse reactions ... 

When topical ophthalmic drugs must be administered to patients who are pregnant, the medications should be administered at minimally effective doses and for as short a time as possible.The use of nasolacrimal occlusion (see Chapter 3) after the instillation of eye medications minimizes systemic drug absorption and should always be recommended. Patients who take medications should also be advised about the potential risks to newborns during breast-feeding (Figure 1-2). Timolol, for example, has been shown to be concentrated in breast milk. 

Early in the development of timolol, some reports indicated the relatively rapid development of tolerance to the drug s ocular hypotensive effects, referred to as escape. The lOP is lower early in the conrse of therapy than with chronic treatment. The lOP resnlts, however, are similar with chronic use of either 0.5% timolol or 0.25% timolol. In addition, the fellow untreated eye may show a decrease in lOP, which most likely resnlts from a consensnal (contralateral) effect. Contralateral effects resnlting from systemic drug absorption can be significant. 

Intravenous bolus (IV) Complete (100%) systemic drug absorption Rate of bioavailability considered instantaneous Drug is given for immediate effect Increased chance for adverse reaction Possible anaphylaxis... 

Intravenous infusion (IV inf) Complete (100%) systemic drug absorption Plasma drug levels more precisely controlled May inject large fluid volumes Requires skill in insertion of infusion set... 

The drug dosage form may also be affected by food. For example, enteric-coated tablets may stay in the stomach for a longer period of time because food delays stomach emptying. If the enteric-coated tablet does not reach the duodenum rapidly, drug release and subsequent systemic drug absorption are delayed. In contrast, enteric-coated beads or microparticles disperse in the stomach, are less affected by food, and demonstrate more consistent drug absorption from the duodenum. 

Bioequivalent drug products are pharmaceutical equivalents whose bioavailability (i.e., rate and extent of systemic drug absorption) does not show a significant difference when administered at the same... 

Systemic drug absorption from a drug product consists of a succession of rate processes (Fig. 2). For solid oral, immediate release drug products (e.g., tablet, capsule), the rate processes include 1) disintegration of the drug product and subsequent release of the drug 2) dissolution of the drug in an aqueous environment and 3) absorption across cell membranes into the systemic circulation. In the... 

Furthermore, the lacrimal fluid flushes out instilled substances from the surface of the eye, and fluid is then drained by the nasolacrimal duct. Systemic drug absorption may also take place through vessels of the conjimctiva or from the nasal cavity after drainage. Thus, the drug is prevented from reaching the anterior part of the eye, and this results in low bioavailability [10]. 

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