The last prescription drug use survey conducted by the CDC1 reported that 45 percent of Americans have used a prescription drug in the last 30 days. While a 2018 Council for Responsible Nutrition consumer survey on dietary supplements sited that 75 percent of US adults take dietary supplements.2 Consider then, that there are over 19,000 FDA approved prescription drug products.3 in the US alone. That’s a dizzying array when you consider that the history of drugs4 only dates to 1898 with the introduction of heroin and the introduction of aspirin the following year.
With all the medicinal drugs and supplements that humans take, how much gets to where it needs to be in the body, and what interactions do these compounds experience throughout their journey? The technical term for this is pharmacokinetics – derived from the Greek pharmakon (drug) and kinetikos (movement) – it's the study of what happens to pharmaceuticals and nutraceuticals when administered to a living organism. In layman's terms, “bioavailability” is a close approximate term that you would have heard. So, let’s dive into this tiny world called pharmacokinetics and ask: what happens in the journey of a supplement or drug throughout the human body?
In a nutshell pharmacokinetics is the study of how an organism affects a drug. While, a separate field of study namely pharmacodynamics, discusses how a drug affects an organism. There are four phases of pharmacokinetics from intake to elimination which are:5 absorption, distribution, metabolism, and excretion (ADME). Let’s start by breaking each down a bit (yes, pun intended).
Absorption is the rate and method that a drug enters the body. This can occur in two ways: enteral and parental. Enteral drugs are orally administered and pass through all or part of the gastrointestinal track. Parental drugs avoid the GI tract such as is the case with IV, inhalation and topical skin treatments. Some enteral drugs only touch upon a small portion of the GI system before entering the bloodstream as is the case with buccal (cheek), sublingual (salivary glands beneath the tongue) or rectally administered medications.
Enteral drug absorption is an extensive and perilous process. Compounds can suffer a series of tragic fates. First, they can be denatured or damaged by gastric acid. Second, food particles can bind or sequester drug molecules. And third which we will cover more in a moment, part of the natural process of pharmacokinetics itself involves chemical altering via enzymes during metabolism. And all these pitfalls can affect the bioavailability (meaning the amount that enters systemic circulation and is therefore able is to have an active effect) of a drug or supplement.
Except for those administered via IV, all drugs must cross a variety of tissue membranes in order to enter the bloodstream. These can include the layers of skin, intestinal (endothelium) lining and capillary walls. Compounds administered orally are absorbed via the stomach and small intestine. From there they travel through the portal venous system on their way to the liver and then onto systemic circulation.6 Which leads us to…
Distribution delineates how these compounds move around the body. Once entering the bloodstream, molecules cross capillary walls and then into tissues before passing through cellular membranes to their final destination of the cell itself.
Metabolism generally refers to the process of breaking down food into energy. In pharmacokinetics, metabolism is weighed in terms of a compound becoming sufficiently water soluble for elimination.7 Metabolism can occur in a variety of organs and tissues, but most often occurs via hepatic metabolism (through the liver).8 Drug metabolism can also occur in the kidneys, gut walls, lungs, skin and blood plasma. In pharmacokinetics hepatic metabolism has two phases. Drugs can be processed either in phase I or phase II or both. Most drugs go through both phases of metabolism.
Phase I involves the chemical alteration of drug molecules via oxidation (most common), or by reduction or hydrolysis. A drug that is metabolized to an altered but still active form is called an active metabolite. Metabolites typically act similarly but less potent to their parent drugs. Although some metabolites are actually stronger and therefore designed to be responsible for the therapeutic action of the drug. Additionally, some medications called prodrugs are inactive until metabolized when they form the active drug as is the case with aspirin.
Phase II further alters the drug or phase I metabolite by attaching it to an ionizable grouping in a process called conjugation. The resulting inactive conjugate is larger and more water soluble thus allowing for easy secretion into bile or urine.9 Any metabolites formed in phase 2 are unlikely to be pharmacologically active.
Excretion pretty self-explanatory, right? All drugs, prodrugs and their metabolites are eventually eliminated. Most compounds are eliminated as water-soluble compounds via the kidneys or liver as urine. Larger lipid-soluble (i.e. fat soluble) compounds require hepatic metabolism (phase I and phase II metabolization) in order to be rendered sufficiently water-soluble. Compounds that enter hepatic circulation can be eliminated via bile through the duodenum and small intestines. During this process, compounds can be reabsorbed from the small intestine and recycled in a process called enterohepatic circulation. Compounds that are not reabsorbed are eliminated typically as feces however they may also be eliminated via bile, gas, sweat, saliva, breast milk, hair, tears, and even exhaled as air.10
That’s quite a remarkable journey. Especially when you consider that it can take minutes for a drug to begin to take effect, although it’s typically it’s around 30 minutes.11 It’s not really surprising then to think that factors like genetics, environment and overall health can create such wide variations in metabolism and bioavailability from one individual to another. And, this is one reason behind why we see variations in blood plasma concentrations as well as a disparity in drug response. Which brings us to liposomes and their ability to weather the storm of pharmacokinetics. Liposomes – tiny microscopic spheres made from lipids and containing various compounds – can change pharmacokinetics in a big way.
While liposomes were originally designed for intravenous delivery, recent technology advancements have allowed for development of truly effective oral liposomal delivery. A 2016 study demonstrated that liposomal encapsulated vitamin C had a higher bioavailability than regular supplements.12 Liposomes, which mimic our own cellular membranes, can improve the pharmacokinetics for their contents – protecting compounds on their journey through digestion and circulation. Liposomes can even be sized for targeting specific organs for optimal uptake of pharmaceuticals and nutraceuticals. Are liposomes the new wave of the medical drug and supplement frontier? An increasing amount of research points to higher bioavailability, uptake, and observed benefits for users.
1https://www.cdc.gov/nchs/products/databriefs/db334.htm
2https://www.crnusa.org/CRNConsumerSurvey
3https://www.fda.gov/about-fda/fda-basics/fact-sheet-fda-glance
4http://www.goodmedicinebadbehavior.org/explore/history_of_prescription_drugs.html
5https://www.pharmacologyeducation.org/clinical-pharmacology/clinical-pharmacokinetics
6https://www.merckmanuals.com/professional/clinical-pharmacology/pharmacokinetics/drug-absorption
8https://www.ionsource.com/tutorial/metabolism/met_slide3.htm
9http://paindr.com/wp-content/uploads/2015/10/Phase-I-and-II.pdf