Answer to Question 1
Before being absorbed from the GI tract into the blood stream, Fred may be metabolized into a different molecule. Once into the blood stream of the portal system, Fred would have to pass through the liver, where he could also be metabolized, before entering the general circulatory system. Once in the general circulatory system, Fred would likely travel to various tissues, and if sufficiently lipid soluble pass into and out of the brain. At some point Fred would likely be metabolized into a water soluble (ionized) molecule, pass in to the kidneys and the urine, where he would be excreted. Fred could still be lipid soluble and get dumped into the bile ducts, where he would get deposited into the feces, where he could be excreted.
Answer to Question 2
When drugs are taken orally, they may be altered enzymatically in the G.I. tract or, more commonly, in the liver before they get into the general circulatory system supplying blood to the rest of the body and brain.
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