Presentation 1

Sudan International University
Faculty of Dentistry
Sara Abdalla
Principles of Pharmacokinetics
Pharmacokinetics
• Pharmacokinetics is derived from two words: Pharmacon
meaning drug and kinesis meaning movement.
• It is ‘what the body does to the drug’. It includes absorption (A),

distribution (D), metabolism (M) and excretion (E) of a drug.
• All these processes involve movement of the drug molecule

through various biological membranes.
Drugs cross various biological membranes by the following
mechanisms:
1. Passive diffusion.
2. Filtration.
3. Specialised transport.
a. Active transport.
b. Facilitated transport.
Passive Diffusion
• Bidirectional process.
• The drug molecules move from a region of higher concentration to lower
concentration until equilibrium is attained.
• The rate of diffusion is directly proportional to the concentration gradient
across the membrane.
• It does not require energy.
• Lipid-soluble drugs are transported across the membrane by passive

Filtration
• Filtration depends on the molecular size and weight of the drug.
• If the drug molecules are smaller than the pores, they filtered
easily through the membrane.
Specialised Transport
1. Active transports:
• The drug molecules move from a region of lower to higher concentration
against the concentration gradient.
• It requires energy.
2. Facilitated transport:
• The drug attaches to a carrier in the membrane, which facilitates its
diffusion across the membrane.
• It does not require energy.
Drug Absorption
• The movement of a drug from the site of administration into the
blood stream.
• Factors influencing drug absorption:
• Physiochemical properties of the drug.
• Route of administration.
• PH and ionisation.
• Food.
• Presence of the other drug.
• Pharmacogenetics factors.
• Area of the absorbing surface.
• Gastrointestinal and other diseases.
Bioavailbility
• It is the fraction of a drug that reaches the systemic circulation
from a given dose.
• Intravenous route of drug administration gives 100% bioavailability,

as it directly enters the circulation.
• Bioequivalent: two formulations of the same drug produce equal

bioavailability
• Bioinequivalent: formulations differ in their bioavailability

Factors Affecting Bioavailability:
• Factors affecting drug absorption also affect bioavailability of a
drug.
• Other factors that affect the bioavailability of a drugs are:
1. First-pass first-pass effect: oral drugs pass via gut wall → portal
vein → liver → systemic circulation.
certain drugs get metabolized and are removed or inactivated before they
reach the systemic circulation.
2. Heptic diseases: They result in a decrease in drug metabolism;
thus increasing the bioavailability of drugs that undergo first-pass
metabolism.
3. Enterohepatic cycling: It increases the bioavailability of drugs
Drug Distribution
• Distribution is defined as the reversible transfer of drugs between
body fluid compartments.
Apparent Volume of Distribution
(aVd)
• Apparent volume of distribution is a hypothetical volume of body fluid
into which a drug is uniformly distributed at a concentration equal to
that in the plasma assuming the body to be a single compartment.
• Drugs with high molecular weight e.g. heparin or drugs extensively

bound to plamsa protein e.g. warfarin are largely restricted to the
vascular compartment; hence their aVd is low.
• Small water soluble molecules are distributed in total body water and
the aVd approximately equals to thr total body water.
Drug Metabloism
• Drug metablosim is a chemical alteration of the drug in a living organism.
• Drug metabloism usually involves conversion of the lipid-soluble and

unionised compounds into water-soluble and ionised compunds to prevent
their reabsorption by renal tubules and enhance their excretion.
• Highly ionised drugs may not get metabolised and excreted as such.
• Sites: live is the main site for drug metablolism; other sites are GI tract,
kidney, lungs, bloos and skin.
Drug metabolism affects the
activity of a drug in different
ways:
1. Active drug to inactive drug.
Phenytoin → p-Hydoxyphenytoin
2. Active drug to active metabolite.

Codeine → Morphine
3. Inactive drug to active metabolite

Prednisone → Prednisolone
Drug Metabolising Enzymes
1. Microsomal Enzymes:
• Mainly present in the endoplasmic reticulum of the cells e.g. cytochrome
P450, glucuronyl transferase.
• Some human CYP 450 genes exhibit polymorphism.
2. Nonmicrosomal Enzymes:
• Mainly found in the cytoplasm, mitochondria of the liver and in plasma.
• Hofmann elimination inactivation of drugs without the need of enzymes

e.g. atracurium - a muscle relaxant undergoes Hofmann elimination.
Factors Affecting Drug
Metabloism
1. Age.
Neonates and elderly metabolise some drugs to a lesser extent than in adults
due to dmimished activity of hepatic microsomal enzymes.
2. Diet.
Poor nutrition can decrease enzyme function.
3. Diseases.
Chronic liver diseases affect hepatic metabolism of some drugs.
4. Genetic factors (pharmacogenetics).
genetic variation of the metablic enzyme can incease or decrease drug
metabolism.
5. Simultaneous administration od drugs.
This can increase or decrease drug metabolism (enzyme induction or inhibition).
Enzyme Induction
• Is the increase in the synthesis of microsomal enzymes due to
administration of certain drugs.
• These drugs are referred as enzyme inducers e.g. rifampicin,

phenytoin, barbiturates, carbamazepine.
Clinical Importance of Enzyme
Induction
1. Treatment failure: enzyme induction may increase the metabolism of
drugs; thus reducing the duration and intesity of their action.
2. Autoinduction and drug tolerance e.g. carbamazepone enhances its

own metabolism.
3. Drug toxicity due to overproduction of toxic metabolite e.g. increased

incidence of hepatotoxicity with paracetamol in alchoholics is due to
overproduction of toxic metabolite og paracetamol.
Enzyme Inhibition
• Is the inhibition of the activity of drug-metabolising enzymes.
• These drugs are referred as enzyme inhibitors e.g. cirpofloxacin,

erythromycin chloramphenicol.
• Clinical relevance of enzyme inhibition: increased incidence of bleeding

with warfarin due to concomitant administration of erthromycin or
cholarmphenicol.
Drug Excretion
• Drug excretion is the removal of the drug and its metabolite from the
body.
• The main channel of excretion of drugs is the kedney. Other sites

include lungs, bile, faeces, sweat, saliva, tears.
• The process involved in the excretion of drugs via kidney are

golmerular filtration, passive tubular reabsorption and active tubular
secretion.
• Glomerular filtration: drugs with smaller molecular size are more readily
filtered.
• Passive tubular reabsorption: the main factor affecting the passive
reaborption is the PH of the renal tubular fluid and the degree of ionisation.
Strongly acidic and strongly basic drugs remain in ionized form at any pH of
urine and hence are excreted in urine.
• Weak acids are more rapidly excreted in alkaline urine, and vice versa.
• Active tubular secretion: it is a carrier mediated active transport that

requires energy and it is not affected by changes in the PH of urine and
protein binding.
• most of the acidic drugs and basic drugs are secreted by the renal tubules.
• The carrier system is nonselective and drugs having similar physiochemical
properties compete for the same carrier system.
Other Pharmacokinetic
Parameters
• Plasma half-life: is the time required for the plasma concentration of
the drug to decrease by 50% of its original value.
• Clnical importance of plasma half-life:

• Determine the duration of drug action.
• Determine the frequency of drug administration.
• Clearance: clearance of a drug is the fraction of the apparent volume

of distribution from which the drug is removed in unit time.

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Sudan International University

• It is ‘what the body does to the drug’. It includes absorption (A),

• All these processes involve movement of the drug molecule

• The drug molecules move from a region of higher concentration to lower

concentration until equilibrium is attained.

• The rate of diffusion is directly proportional to the concentration gradient

across the membrane.

• It does not require energy.

• Lipid-soluble drugs are transported across the membrane by passive

• Filtration depends on the molecular size and weight of the drug.

• Intravenous route of drug administration gives 100% bioavailability,

• Bioequivalent: two formulations of the same drug produce equal

• Bioinequivalent: formulations differ in their bioavailability

• Drugs with high molecular weight e.g. heparin or drugs extensively

• Drug metabloism usually involves conversion of the lipid-soluble and

2. Active drug to active metabolite.

3. Inactive drug to active metabolite

• Hofmann elimination inactivation of drugs without the need of enzymes

• These drugs are referred as enzyme inducers e.g. rifampicin,

2. Autoinduction and drug tolerance e.g. carbamazepone enhances its

3. Drug toxicity due to overproduction of toxic metabolite e.g. increased

• These drugs are referred as enzyme inhibitors e.g. cirpofloxacin,

• Clinical relevance of enzyme inhibition: increased incidence of bleeding

• The main channel of excretion of drugs is the kedney. Other sites

• The process involved in the excretion of drugs via kidney are

• Active tubular secretion: it is a carrier mediated active transport that

• Clnical importance of plasma half-life:

• Clearance: clearance of a drug is the fraction of the apparent volume

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