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Absorption, distribution, metabolism, and excretion 

Absorption, distribution, metabolism, and excretion
Absorption, distribution, metabolism, and excretion

Adrian Kilcoyne

, Daniel O’Connor

, and Phil Ambery

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Subscriber: null; date: 16 October 2017


ADME stands for absorption, distribution, metabolism, and excretion, the 4 key processes that underlie pharmacokinetics. Pathophysiological disorders that affect any stage of this process, and characteristics of a medicine that affect any or multiple stages of this process can impact on the time concentration curve of the medicine and, thus, efficacy and toxicity.

Examples of the impact of the components of ADME and how they may impact on the development process are described below.


For oral drugs, absorption is the extent to which a drug is absorbed from the gut lumen into the portal circulation. Two important features are the rate and extent of absorption. Examples of factors governing drug absorption from the gastrointestinal (GI) tract are shown in Table 3.1.1.

Table 3.1.1 Examples of factors governing drug absorption from the GI tract

Better absorption

Worse absorption

Low molecular weight

High molecular weight

Polar (acidic or basic)


Examples of methods of delivery are shown in Table 3.1.2.

Table 3.1.2 Methods of delivery


Example substance


Digoxin—low molecular weight, polar substance, well absorbed


Bisphosphonates—very high molecular weight, very poorly absorbed, low bioavailability


Testosterone patch—sustained delivery allows for gradual release of testosterone, preferable to injections


Insulin—subject to degradation by stomach enzymes, insulin efficiently absorbed by respiratory mucosa


Distribution refers to the process of the drug moving into and out of the tissues of the body. The volume of distribution relates the concentration of the drug in the plasma to the total amount of the drug in the body. Examples of factors that may impact on volume of distribution are shown in Table 3.1.3.

Table 3.1.3 Factors that may impact on volume of distribution (examples)

Low volume of distribution

Large volume of distribution

Highly protein bound

Low protein binding

Low level of lipophilicity

Highly lipophilic (increased tissue binding)


Metabolism describes the processes (biotransformation) that change the drug into another molecule. In general these processes can be classified as Phase I and Phase II reactions. The liver is the principal organ of drug metabolism. Many examples exist that impact as CYP-450 enzyme inhibitors or inducers, leading to reduced or increased drug concentrations. Four examples are detailed in Table 3.1.4. A fuller list of the main CYP-450 inhibitors/inducers can be found at the online version of the P450 Drug Interaction Table.

Table 3.1.4 Examples of CYP-450 enzyme inhibitors or inducers



Macrolide—erythromycin, clarithromycin

CYP-450 3A4 inhibitors

Fruit juices (cranberry/grapefruit)

Inhibitors of CYP-2C8 / CYP 3A4

Herbal antidepressant (St John’s Wort)

CYP-450 enzyme inducer


CYP-450 enzyme inducer


Excretion describes the processes that remove the drug from the body. A number of routes for drug excretion exist. Examples are given in Table 3.1.5.

Table 3.1.5 Example routes for drug excretion







Renal—Passive filtration


Renal—anionic active transporter


Renal—cationic active transporter


Renal transport inhibitor

Dapafloglozin—SGLT-2 inhibitor

Each aspect of pharmacokinetic (PK) is important in clinical development and we explore each aspect of ADME in pre-clinical and clinical development.