This document discusses the process of pharmacokinetics, which includes absorption, distribution, metabolism, and excretion of drugs in the body. It describes how drugs are absorbed through various routes and distributed to tissues and fluids. Metabolism occurs primarily through cytochrome P450 enzymes in the liver and involves oxidation (Phase I) and conjugation (Phase II) reactions. Excretion of drug metabolites occurs primarily through urine by the kidneys and bile by the liver.

1. Pharmacokinetic
Presented by
Apu Marma
Roll: 566
Department of Pharmacy

2. Content
›Introduction
›Process of pharmacokinetics
–Absorption
–Distribution
–Metabolism
–Excretion

3. Introduction
› Pharmacokinetics (from Ancient Greek pharmakon “drug” and
kinetikos “movement or motion”), sometimes abbreviated as PK, is
a branch of pharmacology dedicated to determine the fate of
substances administered to a living organism. The substances of
interest include any chemical xenobiotic such as: pharmaceutical
drugs, pesticides, food additives, cosmetics, etc. It attempts to
analyze chemical metabolism and to discover the fate of a chemical
from the moment that it is administered up to the point at which it
is completely eliminated from the body. Pharmacokinetics is the
study of how an organism affects a drug, whereas
pharmacodynamics (PD) is the study of how the drug affects the
organism.

4. Process of pharmacokinetics

5. Absorption
›Gastrointestinal tract
–Stomach- by simple diffusion
–Small intestine- by simple diffusion (non-ionized),
filtration ( ionized ) and by active transport
–Rectum- by simple diffusion ( slow and incomplete
absorption )
›Respiratory tract (lungs)
–Rapid absorption due to high surface area of the alveoli
and high vascular supply of the lung.

6. ›Skin
–By passive process (dissolving in cell membrane and
passing through aqueous pores of the cell membrane.
›Muscle and Subcutaneous tissue
–Muscle- by simple diffusion ( rapid and uniform
absorption because vascularity of the muscle is more)
–Subcutaneous tissue- by simple diffusion ( slow
absorption, as fatty tissue is poorly vascularized )

7. Distribution
›The major compartments of drug distribution are:
–Plasma
–Interstitial fluid
–Transcellular fluid ( CSF, synovial, pleural, peritoneal
fluid)
–Intracellular fluid
–Fat

8. Plasma
›Plasma protein binding refers to the degree to which
medications attach to proteins within the blood. A
drug's efficiency may be affected by the degree to
which it binds. The less bound a drug is, the more
efficiently it can traverse cell membranes or diffuse.
Common blood proteins that drugs bind to are
human serum albumin, lipoprotein, glycoprotein,
and α, β‚ and γ globulins.

9. Interstitial fluid
›After a drug enters the systemic circulation, it is distributed
to the body’s tissues. Distribution is generally uneven
because of differences in blood perfusion, tissue binding
(e.g. because of lipid content), regional pH, and
permeability of cell membranes.
›The entry rate of a drug into a tissue depends on the rate of
blood flow to the tissue, tissue mass, and partition
characteristics between blood and tissue. Distribution
equilibrium (when entry and exit rates are the same)
between blood and tissue is reached more rapidly in richly
vascularized areas, unless diffusion across cell membranes
is the rate-limiting step.

10. ›After a drug has entered tissues, drug distribution to
the interstitial fluid is determined primarily by
perfusion. For poorly perfused tissues (e.g. muscle,
fat), distribution is very slow, especially if the tissue
has a high affinity for the drug.

11. Transcellular fluid
› Drugs reach the central nervous system (CNS) via brain
capillaries and cerebrospinal fluid (CSF)
› Some lipid-soluble drugs (e.g. thiopental) enter the brain readily,
polar compounds do not.
› The blood-brain barrier, which consists of the endothelium of
brain capillaries and the astrocytic sheath.
› Drugs may enter ventricular CSF directly via the choroid plexus,
then passively diffuse into brain tissue from CSF. Also in the
choroid plexus, organic acids (e.g. penicillin) are actively
transported from CSF to blood.

12. Metabolism
› Phase-I (P-450)
–The most important enzyme system of phase I metabolism is
cytochrome P-450 (CYP450), a microsomal superfamily of
isoenzymes that catalyzes the oxidation of many drugs.
–Electrons are supplied by NADPH–CYP450
–CYP450 enzymes can be induced or inhibited by many drugs
and substances resulting in drug interactions in which one
drug enhances the toxicity or reduces the therapeutic effect of
another drug.

13. ›Phase- II (Conjugation)
–Glucuronidation, the most common phase II reaction, is the
only one that occurs in the liver microsomal enzyme system.
–Glucuronides are secreted in bile and eliminated in urine.
–Conjugation makes most drugs more soluble and easily
excreted by the kidneys.
–Amino acid conjugation with glutamine or glycine produces
conjugates that are readily excreted in urine but not extensively
secreted in bile.

14. Excretion
›Excretion organs are involved:
–Kidneys (Renal excretion)
–Bile (Biliary excretion)
–Lungs (Pulmonary excretion)
–Saliva (Salivary excretion
–Milk (Mammary excretion)
–Sweat (skin excretion)