A Drug’s Journey Through the Human Body — Part One

You ever wonder how an antibiotic taken by mouth winds up destroying bacteria in your lung? Or how about when you get a headache. Where does a pain killer travel before it gets to your brain to reduce the pain? How do we know that just one milligram of an anti-anxiety drug is enough to calm a nervous adult? Or, how does a drug taken orally get out of the body, or does it?

All the answers to these questions are found in the complex and amazing journey of a drug through the human body. In pharmacological terms, this journey is known as drug pharmacokinetics. If you get a chance, view the 1966 movie Fantastic Voyage. This film touches upon the multiple factors encountered as a substance travels through the human body. For our purposes, we will concentrate on just four major components of drug pharmacokinetics: absorption, metabolism, distribution, and excretion. How a drug produces its action or effects is separately termed drug pharmacodynamics and is not part of this discussion.

For now, let’s focus on the journey of acetaminophen (generic Tylenol), a 500 milligram tablet, when an adult takes this drug by mouth:

Absorption. Most drugs taken by mouth travel from the mouth down the pharynx, past the esophagus, to the stomach, and finally to the duodenum which is part of the small intestine. This circuit is known as the upper gastrointestinal tract or digestive tract. Food follows the same circuit. There are many factors influencing how acetaminophen is absorbed through the duodenum. Some factors include whether you have a healthy duodenum, or if food or other drugs are present during acetaminophen absorption, and a few other factors.

Absorption for differing routes of administration, e.g., rectal, intravenous, transdermal (through the skin), and other routes obviously do not follow the same course for absorption and will be discussed in other articles.

Metabolism. As acetaminophen passes through the duodenal membrane it is taken up by the blood system carrying the drug through the liver. It is in the liver that acetaminophen is metabolized (converted by enzymes) to inactive forms of the drug. Actually, less than 25 milligrams of the original 500 milligrams leaves the liver as active acetaminophen. One by-product of acetaminophen (known as NPAQ) is responsible for acetaminophen toxicity, also termed acetaminophen-induced hepatotoxicity. NPAQ can destroy liver cells, sometimes kidney cells as well.

This is the reason why adult usage of acetaminophen is limited to 4 grams (8 x 500 milligram tablets), or 50 to 75 milligrams per kilogram of a child’s weight per 24 hours.

This includes all forms of acetaminophen—injectable, oral tablet or liquid, and suppositories, as well as combination drug products containing acetaminophen–consumed in a 24-hour period. I would recommend an upper limit of 3 grams (6 x 500mg tablets) or 50 milligrams per kilogram of a child’s weight for a 24-hour period. So, if the child weighs 70 pounds that would be 31.8 kilograms. That means a 70 lb. child could take a maximum of 1600 milligrams of acetaminophen in a 24-hour period.

To prevent or minimize any liver toxicity, acetaminophen is not taken sooner than every four hours. This gives the liver a chance to recharge especially after repeated doses of the drug.

Just think about how many chemicals the liver is being hit with on an hourly basis! For someone with existing liver disease, acetaminophen may not be the best drug for pain relief. For one reason, the diseased liver cannot metabolize acetaminophen at an efficient rate. Even smaller doses of the drug may lead to more liver damage.

Those with even mild liver disease and who also drink alcoholic beverages are increasing the risk of developing severe liver disease when acetaminophen is ingested as well.

All the by -products of acetaminophen, except for NPAQ, produce no effects in the human body and will exit the body mainly by way of the kidneys.

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In the second part of this article, I will discuss acetaminophen’s distribution and excretion (elimination) in the human body.