pharmacokinetic power point presentation by Dr. Bhawana Mehra

1. Basics of Pharmacology w.s.r to
Pharmacokinetics
Guided by: Presentors:
Dr. Bhawana Mehra Priyanshi Samadhiya
Lecturer Department Bharti Barfa
of Dravyaguna
Shubhdeep Ayurved Medical College and Hospital & P.G.
Institute , Indore

2. Pharmacology
Origin of term
Greek Modern Latin
(Drug) Pharmacologia Pharmacology
(early 18th century)
Pharmacon Logos
(Drug/ medicine) (Study)

3. What is Pharmacology?

4. • Deals with interaction of chemical
molecules (Drugs) with living system.
• Includes all aspects of drugs
• Most importantly those that are relevant to
effective and safe use for medicinal
purpose.

5. Scope of pharmacology
• Pharmacokinetics – Movement of
drug
• Pharmacodynamics – effect of drugs
• Pharmacotherapeutics – use of drug
• Toxicology – adverse effects of
drugs.

6. Pharmacokinetics
• Pharmacon kinesis
(Drug ) (Movement )
• This refers to movement of the drug in
and alteration of drug by the body.
• How does the drug concentration change
as it moves through the different
compartment of body
• “ Time course” of Drug in body.

7. Simply it is …….
• Study of the basic processes that determine the
duration and Intensity of drug effect
namely……. ADME i.e.

8. Absorption
Distribution
ExcretionMetabolism

9. Components of Pharmacokinetics
( In VS. Out)
IN
Absorption
Distribution
OUT
Metabolism
Excretion

10. • Absorption – The process of drug
entering into systemic circulation.
• Distribution – The dispersion of a
substance throughout fluids and tissues
of body.
• Metabolism - The transformation of
parent compound into structurally
similar daughter compounds.
• Excretion – The removal of substance
from the body.

11. The interrelation of the ADME of a drug and its
concentration at its site of action

12. Mechanism of transport of drugs
Passive Transport
 Simple Diffusion
 Filteration
 Facilitated
diffusion
Active transport
 Active
Transport
The ADME and action of drug all involve its
passage across cell membrane.
There are varieties of ways for transport of drug.
Endocytosis
and exocytosis

14. Endocytosis Exocytosis

15. Site of Movement of drug Systemic
administration circulation
• Occurs by passive or active transport.
• Rate & extent – depends on Route of
Administration.
• Necessary for the production of a therapeutic
effect.
• IV route – 100% absorption
• For all other routes <100%

16. GIT Liver IVC
Rt. Side of
heart
Lungs
Systemic
circulation
Lt. side of heart
IVOral Inhalation

17. So, absorption is everything
that happens before a drug
enters into systemic
circulation.

18. Absorption of drug by different routes
• IV – 100%
• IM/SC / sublingual - >75% (due to local binding of
drug)
• Oral – low due to
(a) incomplete absorption
(b) first pass metabolism
 Chloroquine ~ 80%
 Bromohexine ~ 20%
 Carbamezapine ~ 70%
 Chlortetracycline ~ 30%

19. Factors affecting rate and extent of absorption of oral
dose
• Disintegration and dissolution time
• Particle size
• Lipid solubility
• pH and ionization
• Concentration
continue……

20. • Area and Vascularity of absorbing
surface
• GI motility
• Presence of food
• Diseases
• Metabolism

21. First Pass metabolism
• Metabolism of drug during its passage from the
site of absorption into systemic circulation.
• “First pass effect” or “ Pre systemic
metabolism”
• All orally administered drug –in intestinal wall
and liver.
• Transdermally administered drug – in skin
• Any other route – in lungs
• Important determinant of oral bioavailability.

22. First pass metabolism of orally administered drug
Oral
Drug
to
systemic
circulation
Destroyed
in gut
Not
absorbed
Destroyed
by gut
wall
Destroyed
by liver

23. Extent of first pass metabolism of some important
drugs
Low Intermediate High
(Not given orally
)
High
( high oral
dose)
Phenobarbitone
Phenylbutazone
Tolbutamol
Theophyline
Aspirin
Quinidine
Chlorpromazine
Pentozocine
Metoprolol
Insuline
Heparine
Isoprenaline
Lignocaine
Hydrocortisone
Testosterone
Propanolol
progesterone
Salbutamol
Morphine
Pethidine
Nitroglycerine

24. Bioavailability
• Fraction (F) of administered dose that reaches
the systemic circulation.
• IV – 100%
• IM/SC / sublingual - >75% (due to local
binding of drug)
• Oral – low due to
(a) incomplete absorption
(b) first pass metabolism

25. • Dispersion of drug throughout the body.
Movment of
drug
• Movement proceed till an equilibrium is
established between two spaces.
Extra Vascular
space viz.
Interstitial space
Fat
tissues
Vascular compartment

26. Factors affecting distribution
• Lipid solubility
• Blood flow
• Ionization
• Plasma protein binding
• Tissue binding

27. Plasma protein binding
• Drugs bound to plasma protein.
Acidic drug to albumin
Basic drug to α1- glyacoprotein
• Binding is reversible
• free fraction - available for action.
• Bound form acts as reservoir
• Make the drug long acting.
e.g. Warfarin – 99%
Morphine – 35%
Lithium - 0%

28. Tissue storage
• Drugs may bound to tissues.
• E.g. – Skeletal muscle, heart & kidney– Digoxin
Liver & Retina - Chloroquine
Thyroid - Iodine
Bone and teeth – Tetracycline
Iris – Ephedrine, Atropin
Adipose tissue – Thiopentene , ether, DDT
• Act as reservoir
• Prolong duration of action.

29. Apparent volume of distribution
• Assumption-
1. body as single homogenous compartment
with volume V.
2. Drugs get uniformly distributed.
Amount of drug in body
Plasma concentration of drug
= 500mg
10mg/liter of plasma
Vd = 50liters
Vd=

30. Importance of Vd
• Highly protein bound drugs largely restricted to
vascular space lower Vd
• Distributed in other tissues high Vd
• In liver and renal disease hypoalbuminemia
PPB reduced free fraction increased
Tissues , fat ,
Interstitial space

31. • Chemical alteration of the drug in the body.
• Non Polar( Lipid soluble) to Polar ( Lipid
insoluble)
• Hydrophilic drugs are excreted unchanged.
• Primary site –
Others are -

32. It may leads to
• Inactivation of active drug
Phenobarbitone hydroxyphenobarbitone
Propanolol 4 hydroxypropanalol
• Active drug to active metabolite/metabolites
Codeine Morphine
Digitoxin Digoxin
Diazapam Oxazapam
• Inactive (Prodrug) to active drug
Levodopa Dopamine
Prednisone Prednisolone
Bacampicillin Ampicillin

33. • Passage out of systemically absorbed drug.
• Drugs may get excreted after metabolism or
unchanged.
• Primarily through–
• Others are – Saliva, Sweat, Milk

34. • Urine – Most important and common channel.
e.g. – aspirin,
• Faeces /bile – for larger molecule (MW> 300)
e.g. – erythromycin, ampicillin, rifampicin
• Intestine – e.g. heavy metals
• Exhaled air – for gases and volatile liquids
e.g.- general anesthetics, alcohol, salbutamol
• Saliva and sweat – e.g. lithium, pot. Iodide,
heavy metals
• Milk – e.g. Tetracyclines, Streptomycine,
Theophylline, Vit A & D.

35. Importance of pharmacokinetics
PK determines the –
• Route of administration
• Dose
• Latency of onset
• Duration of action
• Frequency of drug administration

36. Examples
Aspirin
• Poorly absorbed from stomach and small
intestine.
• Microfining enhance absorption
• Deacetylated in gut wall, liver, plasma and
other tissues.
• ~80% bound to plasma protein
• Vd ~ 0.17L/kg
• Metabolized in – liver
• Excreted by urine.

37. Bromohexine (alkaloid of Adhatoda vasica)
• Poorly absorbed orally
• Extensive first pass metabolism
• Bioavailability ~ 20%
• Plasma protein binding ~ 99%
• Vd~ 5.5 to 7 liter/kg
• Excretion by urine – 1% unchanged and
rest as metabolites.

38. Conclusion
• Pharmocokinetic is study of what body
does with drug viz. absorption,
distribution, metabolism and excretion.
• It is important for determination of route
of administration, dose, latency of onset,
duration of action & frequency of drug
administration