In the recent weeks, I have seen on several groups in which vaccines are discussed how people confuse injection and ingestion and use this term to explain the difference between getting exposed to a chemical from oral route versus vaccine injection route. Indeed, this oversimplification of terms resulted in an unexpected consequence similar to the classical sketch of the evolution of man:
Initially, this sketch was designed to represent the different iterations and species that resulted in the modern man (Homo sapiens). Yet, almost everybody understand this sketch as “Man is descending from apes!”. What was initially aimed to simplify a complex concept (that humans and modern primates are coming from a common ancestor and underwent several evolutionary steps) lead to an oversimplification resulting in a complete misunderstanding of the initial concept.
Same things happened with “ingestion versus injection” claim, putting into competition the “oral route” (per os or PO route) versus all other non-PO routes together (intravenous, intra-arterial, sub-cutaneous, intramuscular).
In this post, I will explain why this trope is wrong due to its oversimplification and explains a key element of pharmacokinetics: bioavailability.
1) Administration routes:
To simplify the concept I have drawn a sketch on my whiteboard (I know, I am not another Jean Monnet but it will make its job for us).
As you may know, we have several administration routes with one considered the gold standard: the intravenous route (IV route). IV route is what we refer in pharmacokinetics as a “vascular route”. This one is the preferred route, for many reasons:
1) You avoid first-pass metabolism
2) The whole amount of drugs injected is found in the circulation (100% bioavailability)
3) You can provide a single administration (IV bolus or shot), or a continuous infusion (constant IV infusion) if needed.
Now this administration has also several limitations and challenges, especially if you are a patient. You need specialized medical staff to install and remove an IV route.
In the other hand, we have other routes that we refer as “extravascular routes”. They are much less invasive, does not require a medical staff and can be self-administered by the patient. We have in these extravascular routes:
* Oral (per os or PO) route
* Sub-cutaneous (SC) route
* Intramuscular (IM) route
Unlike the IV route, these routes will experience a delayed delivery of the drug. In IV route, the maximal concentration is achieved almost immediately (C0). In other routes, it is delayed to a defined time (tmax) with a maximal concentration (Cmax) always lesser than the same dose administered by IV route.
The reason why Cmax is always smaller than the C0 of IV route? The presence of an bioavailability.
Bioavailability is a ratio that determines how much of a drug administered via a non-IV route is getting into the bloodstream versus the amount of drug administered via IV route. By default, the IV route is considered as a 100% bioavailability. It is a complex equation that I will discuss in details here, but by default the bioavailability is always smaller than 100%. You can have variation in the bioavailability between IM, SC and PO routes but once the drug reached the bloodstream, these different routes behave exactly the same than the IV route.
Bioavailability is an important factor to consider because you cannot equate an IM, PO or SC administration to an IV route. You will have much lesser drug getting into the bloodstream by these routes versus an IV route. What always matter is how much drug is found in the bloodstream following administration.
This is also very important to consider when you have some drugs with a black box warnings. Some drugs are dosed to be correctly administered via IM or SC (e.g. Vitamin K), almost never by IV (in the case of Vitamin K, this is the black box warning). By injecting these formulation into IV, you will have an overdose effect.
In other cases scenario, some people are using studies performed in IV administration and then grossly extrapolate these into other routes without taking into account the bioavailability and the amount of drugs found in plasma after administration. This is the case of people trying to make claims made on aluminum, claiming wrongly that the aluminum injected with vaccines (IM, SC) will equate in terms of dose to the amount injected via IV route (this is the case for people on kidney dialysis and being fed via IV bags 24/7). In the case of aluminum, both PO and IM/SC routes are very poor in delivering it into the bloodstream. We estimate it between 0.3% (PO) and 0.6% (IM/SC) of the total amount of aluminum injected to reach the circulation (https://www.ncbi.nlm.nih.gov/pubmed/11322172).