BMS 123 · Common Core (Tronc commun)Section 1.4 · Pharmacokinetics and drug absorption
Section 4 of 27
What controls absorption: the patient and the route
Rank the routes of administration by absorption rate with a reason for each, and explain how blood flow, surface area, contact time, food, first-pass metabolism, genetics and disease change absorption.
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Why this matters
The same drug can be fast, slow or useless depending on how it is given and to whom. A route chosen for speed, such as inhalation or sublingual, behaves quite differently from a swallowed tablet that must survive the gut and the liver. Patients are not identical either: diarrhoea, a recent meal, a genetic difference or a disease of the gut can all move absorption in one direction or the other. This section explains the route ranking and the patient factors behind it, so that the choice of route becomes a reasoned decision rather than a habit.
What you need to know first
You need Unit 1.3 for the idea that only dissolved, unionised, lipophilic molecules cross the membrane easily, and Unit 1.2 for the mechanisms of that crossing.
Words to know (5)
Route of administration
The path by which a drug is introduced into the body, such as oral, sublingual, rectal, intramuscular, subcutaneous, inhaled or applied to the skin. Changing from oral to sublingual can speed up the onset of the same drug.
Contact time
How long the drug remains in contact with the absorbing surface; the longer the contact, the more drug is absorbed. Diarrhoea shortens contact time and so reduces the amount of an oral drug that is absorbed.
Surface area
The total area of absorbing membrane available; a larger area allows a greater rate of absorption. The villi and microvilli of the small intestine give it the largest surface in the gut.
First-pass metabolism
The breakdown of an orally administered drug in the intestine or liver before it reaches the systemic circulation, which reduces the amount that arrives. A drug may lose much of its dose to the liver on the way from the gut to the blood.
Gastric emptying
The speed at which the stomach releases its contents into the small intestine, which sets when most absorption can begin. A high-fat meal slows gastric emptying and delays the peak of an oral drug.
One idea at a timeIdea 1 / 6
In one sentence Absorption is fastest from the lungs and slowest through intact skin, and each intermediate route has its own anatomical reason.
Routes differ greatly in how fast they deliver a drug
The route of administration is one of the most important factors influencing drug absorption. Absorption rate is highest with the inhalation route and lowest with the topical skin route. The order given in the lecture notes is: inhalation, sublingual, rectal, intramuscular, subcutaneous, oral, transdermal, then skin. Inhalation wins because the alveolar membrane has a large surface area, good permeability and extremely high perfusion. Sublingual absorption is rapid because of the large, thin capillary bed under the tongue. Muscle absorbs faster than subcutaneous tissue because blood flow to muscle is better. The skin has a large surface area but is impermeable to most drugs.
For example
A drug given by intramuscular injection is absorbed faster than the same drug injected under the skin, because muscular tissue receives more blood; massage or a hot compress increases that flow further.
Pause and check yourself
Which route gives the fastest absorption, and which gives the slowest?
Show the answer
Inhalation is fastest, because of the large, permeable and richly perfused alveolar surface, and the skin is slowest, because it is impermeable to most drugs.
Read detailed explanations
Why the stomach comes first but the intestine absorbs most
The stomach is the first compartment an oral drug meets, yet it is rarely the main absorbing surface. Three features explain the paradox. First, surface: the gastric mucosa is comparatively smooth, while the small intestine carries villi and microvilli that multiply its area enormously, so far more membrane is available for diffusion downstream. Second, blood flow: the intestine receives a very large share of the cardiac output, which keeps the concentration gradient steep by removing absorbed drug from the membrane. Third, time: the small intestine is long and its contents move relatively slowly, so contact time is longer than in the stomach, whose contents are emptied onward. The stomach nevertheless decides the timing of everything that follows, because gastric emptying is the gate that releases the dose into the absorbing segment. That is why a fatty meal, which slows emptying, delays the peak blood level of most oral drugs even though the intestine would have absorbed them efficiently.
First-pass metabolism as a fraction, and how routes avoid it
First-pass metabolism is easiest to picture as a toll on the road from the gut to the general circulation. Everything absorbed from the small intestine passes through the portal vein into the liver before it reaches the rest of the body, so the liver sees the full arriving dose before any other organ. If the liver and gut wall remove a fraction of that dose, the amount that finally reaches the general circulation is only what survives. Two consequences follow. First, the same molecule given by mouth and by vein can produce very different blood levels, which is exactly why bioavailability is defined against the intravenous route. Second, routes that enter the general circulation without passing the liver can preserve much more of the dose: a sublingual tablet drains into veins under the tongue, a rectal suppository drains partly into veins that bypass the portal system, and an intravenous or intra-arterial injection bypasses absorption entirely. The size of the first-pass loss is not fixed: liver disease, enzyme induction or enzyme inhibition by another drug can all change the fraction removed, and therefore change how much of an oral dose actually arrives.
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Routes ranked by absorption rate
Eight routes arranged from the fastest absorption to the slowest, with the anatomical reason behind each position in the ranking.
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01 / 5Inhalation
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Inhalation
The alveolar membrane combines a very large surface area, good permeability and extremely high perfusion, so an inhaled drug reaches the blood in seconds. This is why inhalation is the fastest route in the ranking.
Schematic ranking, not to scale. The bar lengths are illustrative, not measured; speed also depends on the drug, the formulation and the individual patient.
✓The small intestine is the main oral absorbing site because of its villi and microvilli and its rich blood supply.
✓Blood flow, surface area and contact time set the rate; diarrhoea shortens contact time and lowers absorption.
✓High-fat meals delay absorption by slowing gastric emptying, except for poorly soluble drugs such as griseofulvin.
✓First-pass metabolism in the gut and liver removes part of every oral dose before it reaches the general circulation.
✓Genetics and disease states change absorption from one patient to another.
Go deeper
Worked example
Reasoning from the route to the absorption rate. A patient needs a drug quickly, but is vomiting and cannot swallow a tablet. Three options are discussed: an inhaled form, a sublingual tablet and an intramuscular injection. Rank them by expected absorption rate and explain the anatomy behind the ranking.
Inhalation ranks first: the alveolar membrane is large, permeable and extremely well perfused, so the drug reaches the blood in a very short time.
Sublingual ranks second: the capillary bed under the tongue is large and thin, and the drug also partly avoids the first pass through the liver.
Intramuscular ranks third among these three, but is still faster than subcutaneous injection because muscular tissue has a better blood supply.
The oral route is not usable here because vomiting both prevents swallowing and can expel the dose before any absorption occurs.
Ranking routes is not a memory exercise: each position follows from surface area, permeability, blood flow and the amount of first-pass metabolism the drug avoids.
Common misconception
Many learners assume that the oral route is always the safest and most reliable because it is the most familiar. In fact the oral route has the lowest and most variable absorption of the common routes, and it exposes every dose to gut enzymes and to first-pass metabolism in the liver.
Check your reasoning
A patient starts a course of an oral drug and, a week later, develops severe diarrhoea. Using blood flow, surface area and contact time, explain why the treatment may now work less well even though the patient swallows every dose.
Reveal an answer
Diarrhoea shortens the residence time of the drug in the small intestine, so the contact time at the absorbing surface falls; less of the dose has time to cross the membrane before it is swept onwards. The absorbing surface may also be inflamed and less effective, while the drug still reaches the liver and is subject to first-pass metabolism as usual. The result is a lower concentration in the blood from the same swallowed dose, so the amount absorbed, not the amount taken, has changed.
Where this comes from
BMS 123 General Pharmacology II lecture notes — Part 1, Principles of Pharmacokinetics · Drug absorption: route of administration; patient physiological factors; first-pass metabolism; pharmacogenetic and disease factors
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About this course and its sources
Bilingual lessons organised from the supplied BMS 123 General Pharmacology II lecture notes (Principles of Pharmacokinetics and Principles of Pharmacodynamics). Diagrams are original educational schematics; pharmacology, nursing and French-language review are pending.