1. DRUG
PHAMACOKINETICS
By Amad Islam

2. LIFE HISTORY OF DRUG
Dosage Regimen
Concentration in Plasma
Concentration at the site
of action
Absorption
Distribution
Metabolism
Excretion
Pharmacokinetics
Pharmacodynamics
Effect

3. DEFINATION
WHAT THE BODY DOES TO THE DRUG

6. ABSORBTION OF DRUG

7. ABSORBTION OF DRUG
Absorption is the transfer of a drug from its site of
administration to the blood stream.
Most of drugs are absorbed by
the way of passive transport
 Intravenous administration has
no absorption
Inhalation→Sublingual→Rectal→
intramuscular→subcutaneous→o
ral→transdermal

8. ABSORBTION OF DRUG
Factors affecting absorption
 Drug properties:
lipid solubility, molecular weight, and
polarity etc
 Blood flow to the absorption site
 Total surface area available for absorption
 Contact time at the absorption surface
 Affinity with special tissue

9. ABSORBTION OF DRUG
Points to Remember
 The drugs which are Unionized, low polarity, small
molecule and higher lipid solubility are easy to
permeate membrane(Absorb).
 Acidic drugs re absorbed are largely unionized in
stomach and absorbed faster while basic drugs are
absorbed faster in intestines.
Letrozole is highly
Lipid Solouble and
Basic Compound so
easily completely
absorbed by G.I.T.
Doxorubicin HCL
is Highly water soluble
and Large molecule so
difficultly absorbed by
G.I.T.

10. ABSORBTION OF DRUG
Bioavailability
It is measure of the fraction (F) of administered dose
of a drug that reaches the systemic circulation in the
unchanged form.
 It refers to the rate and extent of absorption.
 Bioavailability of drug injected i.v. is 100%, but is
frequently lower after oral ingestion, because:
 The drug may be incompletely absorbed
 The absorbed drug may undergo first pass metabolism
in intestinal wall and/or liver or be excreted in bile.

11. ABSORBTION OF DRUG
Lorelin (Leuprorelin Acetate) is sophisticated PLGA
microspheres. So, Bioavailability by subcutaneous
administration is comparable to that by intravenous
administration.

12. ABSORBTION OF DRUG
 Bioequivalence is a term used to assess the
expected in vivo biological equivalence of two
proprietary preparations of a drug. If two products
are said to be bioequivalent it means that they
would be expected to be, for all intents and
purposes, the same.

13. BIOAVAILABILITY - AUC
Plasmaconcentration(mcg/ml)
Time (h)0 5 10 15
AUC p.o.
F = ------------ x 100%
AUC i.v.
AUC – area under the
curve
F – bioavailability

14. DISTRIBUTION OF DRUG

15. DISTRIBUTION OF DRUGS
It is the passage of drug from the circulation to the
tissue and site of its action.
The extent of distribution of drug
depends on its lipid solubility, ionization
at physiological pH (dependent on pKa),
extent of binding to plasma and tissue
proteins and differences in regional
blood flow, disease like CHF, uremia,
cirrhosis

16. DISTRIBUTION OF DRUGS
Volume of Distribution (V)
Apparent Volume of distribution is defined as the
volume that would accommodate all the drugs in the
body, if the concentration was the same as in plasma

17. DISTRIBUTION OF DRUGS
 Plasma Protein Binding
Most drugs possess physicochemical affinity
for plasma proteins. Acidic drugs bind to plasma
albumin and basic drugs to α1-glycoprotein
The clinical significant implications of PPB are:
a) Highly PPB drugs are largely restricted to the vascular compartment and tend
to have lower Vd.
b) The PPB fraction is not available for action.
c) There is an equilibration between PPB fraction of drug and free molecules of
drug.
(d) High degree of protein binding makes the drug long acting, because bound
fraction is not available for metabolism, unless it is actively excreted by liver or
kidney tubules.

18.  Plasma Protein Binding of Oxaliplatin is >90%.
 So 10% of 85mg/m2 is administered in to achive
Peak plasma concentration of 1.21mcg/mL.(least
effective conc)
• Plasma Protein Binding of Leuprorelin Acetate is 43% to achive
Mean peak plasma of 54.5 µg/L occur within 1 to 3 hours

19. DISTRIBUTION OF DRUGS
Barriers of Distribution
 Blood Brain Barrier(BBB) limits the entry of non-
lipid soluble drugs in Brain and CSF.
 Placental Barrier(PB) Only lipid soluble Drugs can
penetrate – limitation of hydrophilic drugs.

20. METABOLISM OF DRUG

21. METABOLISM OF DRUGS
It is the Chemical alteration of the drug in the
body.
Aim: to convert non-polar lipid
soluble compounds to polar lipid
insoluble compounds to avoid
reabsorption in renal tubules
Most hydrophilic drugs are less
biotransformed and excreted
unchanged – streptomycin,
neostigmine and pancuronium
etc.

22. BIOTRANSFORMATION - CLASSIFICATION
2 (two) Phases of
Biotransformation:
• Phase I or Non-synthetic –
metabolite may be active or
inactive
• Phase II or Synthetic –
metabolites are inactive
(Morphine – M-6 glucoronide is
exception)

23. METABOLISM OF DRUGS
Enzyme Inhibition
One drug can inhibit metabolism of other – if utilizes
same enzyme
 However not common because different drugs are
substrate of different CYPs
 Some enzyme inhibitors – Omeprazole,
metronidazole, isoniazide, ciprofloxacin and
sulfonamides

24. EXCREATION OF DRUG

25. EXCRETION OF DRUG
Excretion is a transport procedure which the
prototype drug (or parent drug) or other metabolic
products are excreted through excretion organ or
secretion organ
Routes of drug excretion
• Kidney
• Biliary excretion
• Sweat and saliva
• Milk
• Pulmonary

26. EXCRETION OF DRUG
Hepatic Excretion
Drugs can be excreted in
 bile, especially when the are conjugated with –
glucuronic Acid
Renal Excretion
 Acidic urine
 alkaline drugs eliminated
 acid drugs reabsorbed
 Alkaline urine
 acid drugs eliminated
 alkaline drugs absorbed

27. KINETICS OF ELIMINATION
 Clearance: The clearance (CL) of a drug is the theoretical volume of plasma
from which drug is completely removed in unit time.
 Ability of organs of elimination (e.g. kidney, liver) to “clear” drug from the
bloodstream
 Plasma half- life time taken for its plasma concentration to be reduced to half
of its original value – 2 phases rapid declining and slow declining.
t1/2 = In2/k
Half Life of Oxaliplatin – 391 hrs……… Dose frequency 12
cycles of 2 weeks

28. KINETICS OF ELIMINATION
 First Order Kinetics (exponential): Rate of
elimination is directly proportional to drug
concentration, CL remaining constant
 Constant fraction of drug is eliminated per unit time
 Zero Order kinetics (linear): The rate of
elimination remains constant irrespective of
drug concentration
 CL decreases with increase in concentration
 Alcohol, theophyline, tolbutmide etc.

29. EXCRETION - THE PLATUE PRINCIPLE
Repeated dosing:
• When constant dose of
a drug is repeated before
the expiry of 4 half-life –
peak concentration is
achieved after certain
interval
• Balances between dose
administered and dose
interval

30. WHY DO WE DO IT?

31. DRUG SAFETY AND EFFECTIVENESS
 Not all people respond to a similar dose of a drug in the exact same
manner, this variability is based upon individual differences and is
associated with toxicity. This variability is thought to be caused by:
 Pharmacokinetic factors contribute to differing concentrations of
the drug at the target area.
 Pharmacodynamic factors contribute to differing physiological
responses to the same drug concentration.
 Unusual, idiosyncratic, genetically determined or allergic,
immunologically sensitized responses.

32. TARGET LEVEL STRATEGY
 Low safety margin drugs (anticonvulsants,
antidepressants, Lithium, Theophylline etc. – maintained
at certain concentration within therapeutic range
 Drugs with short half-life (2-3 Hrs) – drugs are
administered at conventional intervals (6-12 Hrs) –
fluctuations are therapeutically acceptable
 Long acting drugs:
 Loading dose: Single dose or repeated dose in quick
succession – to attain target conc. Quickly
 Loading dose = target Cp X V/F
 Maintenance dose: dose to be repeated at specific
intervals

33. MONITORING OF PLASMA
CONCENTRATION
 Useful in
 Narrow safety margin drugs – digoxin, anticonvulsants,
antiarrhythmics and aminoglycosides etc
 Large individual variation – lithium and antidepressants
 Renal failure cases
 Poisoning cases
 Not useful in
 Response mesurable drugs – antihypertensives, diuretics
etc
 Drugs activated in body – levodopa
 Hit and run drugs – Reseprpine, MAO inhibitors
 Irreversible action drugs – Orgnophosphorous compounds

34. PROLONGATION OF DRUG ACTION
 By prolonging absorption from the site of action –
Oral and parenteral
 By increasing plasma protein binding
 By retarding rate of metabolism
 By retarding renal excretion