Pharmacokinetics is the study of how the body affects drugs over time through absorption, distribution, metabolism, and excretion. Drugs move into, within, and out of the body through various transport mechanisms like passive diffusion, facilitated diffusion, and active transport. Factors like plasma protein binding, organ function, and route of administration influence a drug's absorption, distribution to tissues, metabolism by the liver, and excretion by the kidneys, lungs, bile, sweat, saliva or breast milk. Understanding these pharmacokinetic principles is important for predicting how drugs will behave in the body.

1. PHARMACOKINETICS
 Is the study of the absorption, distribution, metabolism and excretion
of drugs. i.e. the movement of drugs into, within and out of the body.
 For a drug to produce its specific response, it should be present in
adequate concentrations at the site of action.

4. BASIC MECHANISMS OF MEMBRANE TRANSPORT :
Transporters versus Channels: Both channels and
transporters facilitate the membrane permeation of
inorganic ions and organic compounds. In general,
channels have two primary states, open and closed.
The basic mechanisms involved in solute transport across
biological membranes include passive diffusion, facilitated
diffusion, and active transport.
Filtration: The rate of filtration depends both on the
existence of a pressure gradient as a driving force and on
the size of the compound relative to the size of the pore
through which it is to be filtered. In biological systems, the
passage of many small water-soluble solutes through
aqueous channels in the membrane is accomplished by
filtration

5.  Passive Diffusion: Simple diffusion of a solute across
the plasma membrane consists of three processes:
partition from the aqueous to the lipid phase, diffusion
across the lipid bilayer, and repartition into the
aqueous phase on the opposite side.
 Facilitated Diffusion. Diffusion of ions and organic
compounds across the plasma membrane may be
facilitated by a membrane transporter. Facilitated
diffusion is a form of transporter-mediated membrane
transport that does not require energy input. Just as in
passive diffusion, the transport of ionized and un-
ionized compounds across the plasma membrane
occurs down their electrochemical potential gradient.

6.  Active Transport: Active transport is the form of
membrane transport that requires the input of energy. It is
the transport of solutes against their electrochemical
gradients, leading to the concentration of solutes on one
side of the plasma membrane and the creation of potential
energy in the electrochemical gradient formed. Active
transport plays an important role in the uptake and efflux
of drugs and other solutes.
 Ion Pair Transport: Absorption of some highly ionized
compounds is carried here. These compounds are known
to penetrate the lipid membrane despite their low lipid–
water partition coefficients. It is postulated that these
highly lipophobic drugs combine reversibly with
endogenous compounds as mucin in the gastrointestinal
lumen, forming neutral ion pair complexes; it is this
neutral complex that penetrates the lipid membrane by
passive diffusion.

7.  Endocytosis: Endocytosis involves the cellular uptake
of exogenous molécules or complexes in side plasma
membrane– derived vesicles. This process can be
divided into two major categories:
(1) adsorptive or phagocytic uptake of particles
that have been bound to the membrane
surface and
(2) fluid or pinocytotic uptake, in which the
particle enters the cell as part of the fluid phase.
The solute within the vesicle is released
intracellularly

8.  The systemic circulation distributes drugs to various body tissues or
target sites. Drugs interact with specific receptors during
distribution. Some drugs travel by binding to protein (albumin) in
the blood.
 FACTORS INFLUENCING DRUG DISTRIBUTION: Distribution is
the delivery of drug from the systemic circulation to tissues.Once a
drug has entered the blood compartment, the rate at which it
penetrates tissues and other body fluids depends on several factors.
These include
 (1) capillary permeability,
 (2) blood flow–tissue mass ratio (i.e., perfusion rate),
 (3) extent of plasma protein and specific organ binding,
 (4) regional differences in pH,
 (5) transport mechanisms available, and
 (6) the permeability characteristics of specific tissue membranes.

9. BINDING OF DRUGS TO PLASMA PROTEINS
 Most drugs found in the vascular compartment are
bound reversibly with one or more of the
macromolecules in plasma. Although some drugs simply
dissolve in plasma water, most are associated with plasma
components such as albumin, globulins, transferrin,
ceruloplasmin, glycoproteins, and - and -lipoproteins.
While many acidic drugs bind principally to albumin,
basic drugs frequently bind to other plasma proteins, The
extent of this binding will influence the drug’s
distribution and rate of elimination because only the
unbound drug can diffuse through the capillary wall,
produce its systemic effects, be metabolized, and be
excreted.

10. PHYSIOLOGICAL BARRIERS TO DRUG DISTRIBUTION:
 Blood-Brain Barrier: The capillary membrane between the
plasma and brain cells is much less permeable to water-
soluble drugs than is the membrane between plasma and
other tissues. Thus, the transfer of drugs into the brain is
regulated By the blood-brain barrier.
 Placental Barrier: The blood vessels of the fetus and mother
are separated by a number of tissue layers that collectively
constitute
 The placental barrier. Drugs that traverse this barrier will
reach the fetal circulation. The placental barrier, like the
blood-brain barrier, does not prevent transport of all drugs
but is selective.
 Blood-Testis Barrier: The existence of a barrier between the
blood and testes is indicated by the absence of staining in
testicular tissue after the intravascular injection of dyes.

11.  Both metabolism and excretion can be viewed as processes
responsible for elimination of drug (parent and metabolite)
from the body. Drug metabolism changes the chemical
structure of a drug to produce a drug metabolite, which is
frequently but not universally less pharmacologically active.
 Metabolism also renders the drug compound more water
soluble and therefore more easily excreted. Drug metabolism
reactions are carried out by enzyme systems that evolved over
time to protect the body from exogenous chemicals.
 The enzyme systems for this purpose for the most part can be
grouped into two categories: phase I oxidative or reductive
enzymes and phase II conjugative enzymes

12.  RENAL EXCRETION: Although some drugs are excreted
through extra renal pathways, the kidney is the primary
organ of removal for most drugs, especially for those that
are water soluble and not volatile. The three principal
processes that determine the urinary excretion of a drug
are glomerular filtration, tubular secretion, and tubular
reabsorption(mostly passive back-diffusion). Active
tubular reabsorption also may have some influence on the
rate of excretion for a limited number of compounds.
 BILIARY EXCRETION: The liver secretes about 1 L of bile
daily. Bile flow and composition depend on the secretory
activity of the hepatic cells.

13. PULMONARY EXCRETION:
 Any volatile material, irrespective of its route of
administration, has the potential for pulmonary
excretion.
 Certainly, gases and other volatile substances that
enter the body primarily through the respiratory
tract can be expected to be excreted by this route.
 The rate of loss of gases is not constant; it
depends on the rate of respiration and pulmonary
blood flow.

14. EXCRETION IN OTHER BODY FLUIDS:
Sweat and Saliva:
 Excretion of drugs into sweat and saliva occurs but has only
minor importance for most drugs. The mechanisms involved in
drug excretion are similar for sweat and saliva.
 Excretion mainly depends on the diffusion of the un-ionized
lipid-soluble form of the drug across the epithelial cells of the
glands.
Milk:
 Many drugs in a nursing mother’s blood are detectable in her
milk. The ultimate concentration of the individual compound in
milk will depend on many factors, including the amount of
drug in the maternal blood, its lipid solubility, its degree of
ionization, and the extent of its active excretion.