Absorption, Distribution, Metabolism and Elimination (ADME) ​Part 1

What is pharmacokinetics, and what does ADME stand for?

Pharmacokinetics describes what the body does to a drug over time. ADME means Absorption, Distribution, Metabolism and Excretion.

How do potency and efficacy differ?

• Potency: the concentration or dose needed for a given effect. A lower EC₅₀ indicates greater potency.

• Efficacy: the maximum response a drug can produce.

What is the difference between NOAEL and LOAEL?

• NOAEL: highest tested dose with no observed adverse effect compared with controls.

• LOAEL: lowest tested dose with an observed adverse effect compared with controls.

What is absorption, and which administration route bypasses it?

Absorption is movement from the administration site into the bloodstream. Intravenous administration bypasses absorption because the drug enters the blood directly.

How do passive diffusion and active transport differ?

• Passive diffusion: movement down a concentration gradient.

• Active transport: transporter-mediated movement that can occur against a concentration gradient.

What is the difference between paracellular and transcellular absorption?

• Paracellular: between adjacent epithelial cells.

• Transcellular: through cells, crossing their apical and basolateral membranes.

Which form of a drug generally crosses lipid membranes more readily?

The unionised form. The ionised form generally crosses poorly by passive diffusion.

What happens to a weak acid in an acidic environment?

It gains a proton, favouring HA, the unionised form. This favours passive membrane diffusion, all else equal.

What happens to a weak acid in an alkaline environment?

It loses a proton, favouring A⁻, the ionised form. This reduces passive membrane diffusion.

What happens to a weak base in acidic versus alkaline conditions?

• Acidic: protonation favours the ionised form, BH⁺.

• Alkaline: the unionised form, B, becomes more prevalent and crosses lipid membranes more readily.

What is ion trapping?

Drug accumulation in a compartment where the local pH favours its ionised, poorly membrane-permeable form.

On which side of a pH gradient do weak acids and weak bases accumulate?

• Weak acids: the more alkaline side.

• Weak bases: the more acidic side.
  That is where each becomes more ionised.

Besides ionisation, what factors influence absorption?

Drug size, lipophilicity and solubility, plus the absorption site's surface area and blood supply. Food and other medicines can also alter absorption.

What does oral bioavailability describe?

The fraction of an oral dose that reaches the systemic circulation.

What is first-pass metabolism?

Metabolism in the intestinal wall and liver before an absorbed oral drug reaches the systemic circulation, reducing its bioavailability.

Why can oral bioavailability be low?

Key reasons include poor dissolution or absorption, degradation in the gastrointestinal tract, interactions that prevent absorption, and first-pass metabolism.

How does AUC help assess bioavailability?

AUC, the area under the plasma concentration–time curve, measures systemic drug exposure. Bioavailability assessment compares oral and intravenous exposure, accounting for the doses given. IV bioavailability is 100%.

What is Cmax, and how does it differ from AUC?

• Cmax: the highest measured plasma or serum drug concentration after a dose.

• AUC: exposure across the measured time course.

What is drug distribution?

Movement of a drug from the bloodstream into tissues.

Which factors determine how quickly a drug enters a tissue?

Tissue blood flow, tissue mass and the drug's partition characteristics between blood and tissue.

Which plasma proteins commonly bind acidic and basic drugs?

• Acidic drugs: mainly albumin, for example warfarin.

• Basic drugs: often α₁-acid glycoprotein and lipoproteins, for example propranolol.

Which drug fraction can passively diffuse from plasma into tissues?

The free, unbound fraction. Protein-bound drug cannot directly diffuse in this way, but reversible binding allows it to dissociate.

How can tissue binding affect drug action and toxicity?

Tissues can act as a reservoir, releasing drug as plasma concentrations fall and prolonging its effects. Tissue accumulation can also cause toxicity.

How does perfusion affect distribution speed?

Highly perfused tissues, such as the liver, generally equilibrate more quickly. Poorly perfused tissues, such as fat, generally equilibrate more slowly.

What is the apparent volume of distribution, Vd?

The theoretical volume needed to contain the amount of drug in the body at its measured plasma concentration:

Vd = amount of drug in the body ÷ plasma drug concentration

What are the usual units of Vd?

Litres (L) or litres per kilogram (L/kg).

If the body contains 1,000 mg of drug and the plasma concentration is 10 mg/L, what is Vd?

Vd = 1,000 mg ÷ 10 mg/L = 100 L.

What do a low and a high Vd suggest?

• Low Vd: a relatively large proportion of drug remains in the circulation.

• High Vd: a relatively large proportion distributes into or binds to tissues.

Why can Vd exceed the body's actual fluid volume?

Vd is an apparent volume, not an anatomical space. Strong tissue binding lowers plasma concentration, making the calculated Vd very large.

What body-fluid volumes provide useful reference points for Vd in a 70 kg adult?

Approximately:

• Plasma: 4 L

• Extracellular fluid: 14 L, including plasma

• Intracellular fluid: 28 L

• Total body water: 42 L, or 0.6 L/kg