Affiliation:
1. Clinical Bioavailability, Searle Research and Development, Division ofG.D. Searle & Co., Skokie, Illinois
Abstract
A recent important advance in biopharmaceutics has been the utilization of controlled delivery of drugs to the systemic circulation through the intact skin. With the conventional tablet and capsule dosage forms, the amount of drug absorbed through the gastrointestinal (GI) tract varies depending on the quan tity and types of food in the stomach, on the GI motility and transit time. Acid and/or alkaline labile drugs may be deactivated prior to absorption from the GI tract while some drugs also get deactivated by GI microbial flora. In the case of drugs with a high hepatic extraction ratio, the absorbed drug may be largely deactivated by first-pass metabolism before reaching the systemic circulation. Drug absorption through the GI tract can therefore result in variable and/or unpredictable blood levels. Some of this variability can be minimized by administering controlled-release tablet or capsule formulations. However, these dosage forms cannot eliminate the inherent variability associated with first-pass metabolism.
Subject
Cardiology and Cardiovascular Medicine
Cited by
72 articles.
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