Final answer:
The most likely cause of a dramatic decrease in systemic availability of a drug following oral administration is first-pass metabolism in the liver, which can significantly metabolize the drug before it enters the bloodstream.
Step-by-step explanation:
A dramatic decrease in the systemic availability of a drug following oral administration is most likely due to first-pass metabolism in the liver. When a drug is taken orally, it passes through the gastrointestinal (GI) tract and then through the liver before reaching the systemic circulation. The liver is capable of metabolizing the drug, which can greatly reduce its concentration before it reaches the bloodstream. This phenomenon is known as the first-pass or presystemic metabolism. In contrast, increased gastric emptying and enhanced absorption in the small intestine would likely increase drug availability, while reduced drug excretion in the kidneys would slow the elimination of the drug, potentially leading to higher plasma levels, but not affect its initial availability after oral administration.