PHARMACOKINETICS

(Absorption)

Dr. Erejuwa O.O.

Department of Pharmacology and Therapeutics,
Faculty of Basic Clinical Sciences,
Ebonyi State University

Introduction
Pharmacokinetics is a word derived from 2 Greek words – ‘Kinesis’ (which means movement) and
‘Pharmacon’ (which means drug). That is, the movement of drug in the body. Pharmacokinetics can,
therefore be defined as the movement of the drug in and alteration of the drug by the body. It refers to
what the body does to the drug or the effect of the body on the drug. The intensity of drug response is
dependent on the concentration of the drug at the site of action, which in turn is influenced by the
pharmacokinetic properties of the drug. Pharmacokinetics involves 4 processes (parameters), namely:
absorption, distribution, metabolism and excretion.

Absorption
Absorption can be defined as the movement or passage of the drug from its site of administration into
the systemic circulation. When a drug is administered, the entire amount or a fraction/percentage of the
administered drug is absorbed. Administered drugs (except when administered via intravenous route)
usually cross biological membranes and this affect the rate of drug absorption.

Transport across biological membranes

The biological membrane is a bilayer of phospholipid and cholesterol, comprising polar group at the two
surfaces and non-polar group embedded in the matrix. This makes the membranes relatively
impermeable. Transportation of drugs across the membranes occurs by:

i. Passive diffusion
ii. Filtration
iii. Specialized transport

(i) Passive diffusion

Passive diffusion is the process by which the drug diffuses (or moves / passes) across the cell
membrane in the direction of its concentration gradient (that is, from a region of higher concentration to
a region of lower concentration), the membrane playing no active role in the process. It is the most

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important transport mechanism of drugs through membranes. Majority of drugs are transported through
this transport mechanism. Lipid soluble drugs diffuse by dissolving in the lipoidal matrix of the
membrane. The rate of transport is proportional to the lipid: water partition coefficient of the drug. A
more lipid-soluble drug attains higher concentration in the membrane and diffuses quickly. The pH
plays an important role in drug transport. Most drugs are weak electrolytes (that is, their ionization is pH
dependent). Weakly acidic drugs such as sodium phenobarbitone ionize more at alkaline pH whereas
weakly basic drugs such as atropine sulphate ionize more at acidic pH. Lipid soluble non-electrolytes
such as ethanol readily cross biological membranes and the transport is pH independent.

(ii) Filtration
It is the passage of drugs through aqueous pores (aquaporins) in the membrane or through paracellular spaces.
Lipid insoluble drugs cross biological membranes by filtration if their molecular size is smaller than the diameter
of the pores. Most cells in the body including mucosa cells have small pores and drugs with molecular size > 100
or 200 daltons are unable to penetrate. However, capillaries (except those in the brain) have large paracellular
spaces and most drugs (albumin) are able to filter through.

(iii) Specialized transport

Specialized transport can be carrier mediated transport or pinocytosis

(a) Carrier transport

Cell membranes express different types of transmembrane proteins which serve as carriers or transporters for
physiologically important ions, nutrients, metabolites, transmitters, etc across the membrane. At some sites,
certain transporters also translocate xenobiotics including drugs and their metabolites. The cell membrane also
expresses channels. These channels open for a finite time and allow passage of specific ions. These channels are,
however, different from carriers or transporters. The carriers or transporters combine transiently with their
substrate (ion or organic compound) and undergo a conformational change carrying the substrate to the other side
of the membrane where the substrate dissociates and the transporter returns to its original state. Carrier transport
is specific for the substrate, saturable, competitively inhibited by analogues which utilize the same transporter and
is much slower that the flux through channels. There are two types of carrier transport depending on the
requirement of energy

 Facilitated diffusion: In facilitated diffusion, the transporter (belonging to the solute carrier (SLC)
transporters) operates passively without the requirement of energy and translocates the substrate in the
direction of its electrochemical gradient (from a region of higher concentration to a region of lower
concentration). Poorly diffusible substrates are transported via this process. For instance, the entry of
glucose into muscle and fat cells by the glucose transporter, GLUT 4.

 Active transport: It involves transport of substrate against its electrochemical gradient (from a region of
lower concentration to a region of higher concentration) resulting in the selective accumulation of

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 substrate on one side of the membrane. It requires energy. The body has also developed some non-
selective transporters like P-glycoprotein to deal with xenobiotics.

(b) Pinocytosis
It is the process of transport across the cell in particulate form by formation of vesicles. This is applicable to
proteins and other large molecules.

In addition to biological membranes, other factors that affect absorption include:

Aqueous solubility:
Drugs given in solid form must dissolve in the aqueous biophase before they are absorbed. For poorly water
soluble drugs such as aspirin, the rate of dissolution determines the rate of absorption. Ketoconazole dissolves at
low pH. Hence, gastric acid is needed for its absorption. A drug given as water solution is absorbed faster than
when the same drug is given in solid form or as oily solution.
Concentration:
Passive diffusion (of drugs) depends on concentration gradient. A drug given as concentrated solution is absorbed
faster than when given as dilute solution.
Area of absorbing surface:
The larger the surface area, the faster is the absorption and vice versa.
Vascularity of the absorbing surface:
Blood circulation removes the drugs from the site of absorption and maintains the concentration gradient across
the absorbing surface. Increased blood flow increases drug absorption.
Route of drug administration:
The route of drug administration affects drug absorption because each route has its own advantages.