ABSTRACT
INTRODUCTION Most drugs are taken orally. For those intended to act systemically, this route is not always the most efficient due to the numerous anatomic and physiologic barriers that drugs can encounter from the time of ingestion until the time of entry into the general circulation. As a consequence, before the drug enters the circulation and elicits its effects in the target tissue(s), significant loss of the original dose can occur as drug passes, sequentially, through the gastrointestinal (GI) tract, the liver, and the cardiopulmonary system. For some drugs, these barriers can even preclude their use as oral agents. Isoproterenol, dihydroergotamine, lidocaine, nitroglycerin, fentanyl, and naloxone are examples of drugs that suffer from a high first-pass effect, which refers to the loss of drug as the dose passes, for the first time, through organs of elimination during transit from the site of administration to the systemic circulation (1). Processes known to cause significant loss of active drug during first pass include incomplete release from the dosage form, degradation in the GI lumen, poor permeation through the GI wall, active export into the GI lumen, biliary excretion, and metabolism. Of these processes, only metabolism can take place in all of the aforementioned organs.
