Orally delivered drugs

Most drugs are delivered at sites that are remote from their sites of action. Although the most convenient route of administration is the oral route, this presents significant challenges to the delivery of a drug molecule. Clearly, in order to be effective, an orally delivered drug must avoid several potential barriers. For example, it must ... 

The midazolam example shows that gut wall cytochrome P450 can contribute significantly to the attenuation of oral bioavailability of substrate drugs. In addition, the variability and site dependence of expression of the major intestinal CYPs can lead to significant effects on the disposition of orally delivered drugs. 

FIGURE 3.4 Representative plasma concentration vs. time plot for an orally delivered drug... 

Inclusion of the dose sizes in Equation 7.22 is necessary only if the two doses, D0route and /)0IV, are not equal. If all variables in Equation 7.21 are already known, AUC for an orally delivered drug can be quickly calculated with Equation 7.23. 

Despite its popularity, oral delivery would be worthless if it were unable to sustain consistent Cp levels over time. When spaced properly with a correct dose, orally delivered drugs can... 

Liver damage is especially relevant for orally delivered drugs. Why ... 

It will be of interest in the future to contrast the success of enzyme replacement that requires infusion with orally delivered drugs for the treatment of Gaucher s and Fabry s diseases. Oral drugs are clearly more convenient however, the side effects and long-term toxicity must be determined. 

The administration of drugs to ease disease and chronic, severe pain or to provide benefits such as hormone replacement therapy is difficult because drugs taken orally may lose much of their potency in the harsh conditions of the digestive system. In addition, they are distributed throughout the entire body, not just where they are needed, and side effects can be significant. Recently, however, techniques have been developed to deliver drugs gradually over time, to the exact location in the body where they are needed, and even at the time when they are needed. 

Gan, L.-S. L., Thakker, D. R., Applications of the Caco-2 model in the design and development of orally active drugs elucidation of biochemical and physical barriers posed by the intestinal epithelium, Adv. Drug Deliv. Rev. 1997, 23, 77-98. 

It is a general requirement for an optimal therapeutic effect that the active pharmaceutical ingredient (API) is delivered to the site of action in order to provide effective but not toxic concentration levels. Therefore, studies to measure BA are of great importance in order to support new drug product applications. Thus, data on the BA of orally administered drug products is a general requirement to the development... 

There are oral formulations that deliver drug to the lower intestine. In mesalazine 5-amino-salicylic acid is formulated in a polymer-coated oral preparation. Olsalazine is a dimer of 5-aminosalicylate linked by an azo bond. Balsalazide is delivered to the colon where it is cleaved by bacterial azoreduction to release equimolar quantities of mesalazine and 4-aminobenzoyl-/i-alanine. The newer 5-ASA preparations were shown to be superior to placebo and tended towards therapeutic benefit over sulfasalazine. However, considering their relative costs, a clinical advantage to using the newer 5-ASA preparations in place of sulfasalazine appears unlikely. 

To avoid the side effects of sulfapyridine, various preparations to target 5-ASA directly to sites of disease have been formulated. Also known as mesalamine, 5-ASA has been formulated in oral forms (Pentasa, Asacoi). Pentasa is a time-release capsule that releases the drug throughout the GI tract. Asacoi is a pH-dependent-release preparation that delivers drug to the distal small bowel and colon. The response of ulcerative colitis to this formulation appears to be identical to that seen with sulfasalazine. Mesalamine can also be administered as a suppository (Canasa) or enema (Rowasa) for distal colonic disease. 

There are few occasions where a drug is delivered alone in a pure form into the body, but it is usually combined with other materials (called excipients) to form drug delivery systems ( medicines , formulations or dosage forms ). These promote accurate dosing, therapeutic effectiveness, stability and patient acceptability. By far the most common route for delivering drugs into the body is by the oral route, swallowing a tablet or capsule. 

When delivered parentally or orally, a drug in solution is more rapidly bioavailable compared to a solid dosage form. The cosolvent approach also has some limitations as pointed out for other solubilization techniques. When solubilization of a drug is achieved by use of cosolvent, it must meet certain requirements, such as nontoxicity, compatibility with blood, nonsensitizing, nonirritating, and above all physically and chemically stable and inert. 

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