[Sciences/Pharmacology] Ingestion versus injection explained to my cat

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.

2) 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 (

7 replies on “[Sciences/Pharmacology] Ingestion versus injection explained to my cat”

The study you link to contains the following: “All intramuscularly injected Aluminium, e.g vaccines, may eventually be absorbed.” That is IN DIRECT CONTRADICTION TO WHAT your article claims. Please address this issue rapidly in order to keep credibility. Thanks.


Hi Andrej,
Thanks for your comment. Can you point out where did I make my claim wrong? Yes, everything will be absorbed at some point, but what matter is the “rate” (aka “ka” or absorption rate, how fast a substance is absorbed) and “extent” (usually we refer as “F” or bioavailability that is the product of hepatic bioavailabity (F’) and gut bioavailability (Fg)).

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I am not saying that your claim is wrong,I am not an expert in the field. I am just pointing to the inconsistency between your article’s claim: “We estimate it between 0.3% (PO) and 0.6% (IM/SC) of the total amount of aluminum injected to reach the circulation” and the other statement that all of it will be absorbed. So, to clarify, where does the 99,4 or 99,7 procent go if it never reaches the blood? And what does it mean to be completely absorbed in this context?


Hi Andrej, thank you for your message. This is where the rate of absorption comes in hand. We have two limiting factors that makes the aluminum salts (here i refer to the hydroxide or phosphate alike, as they have similar chemical behavior) slowly absorbed over time.
The first bottleneck is the dissolution rate of these salts. Aluminum salts dissolve following this chemical equation (in this case aluminum hydroxide):
Al(OH)3 (s)Al3+ + 3 OH-
As you can see it is an incomplete reaction that is driven by the “mass action law” that I learnt in HS: to push the reaction to the right, you have to deplete one of the two products from the system.
At physiological pH (7.4), these salts are very slowly dissolving because this is where the Ks (solubility constant) is the lowest (you can google that easily). Thats explain one part of the problem.
The second part of the problem is that the injection site (commonly intramuscular) is a poorly perfused organ. You have a dense tissue with very small caliber vessels irrigating them. It will take time to have these compound to reach the circulation and therefore been cleared from the injection site. The best analogy I can bring on is the steak marinade. You may know that the best marinade has to occur overnight because the infusion inside the meat is a very slow process.
To conclude, you have an adjuvant that is non-metabolizable, slowly dissolving and slowly entering the systemic circulation. This results in such a low bioavailability. However, aluminum over time will get dissolved and all of it will get cleared. Thats what all studies have shown.
Now, having such adjuvants that is slowly dissolving is not a big concern because the amount entering the systemic circulation is not enough to increase the total aluminum level in plasma (remember we get exposed daily from our food and water).
What I found surprising from the Avers is they are all concerned about metals being injected under the skin but very conveniently ignore the elephant in the room that are tattoos. Tattoos are long-lasting inoculations of dyes containing various sort of metals that are almost not cleared at all, with our knowledge of their biological fate largely unknown.

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