2. LIFE HISTORY OF DRUG
Dosage Regimen
Concentration in Plasma
Concentration at the site
of action
Absorption
Distribution
Metabolism
Excretion
Pharmacokinetics
Pharmacodynamics
Effect
5. DRUG R&D
Drug discovery and development
•10-15 years to develop a new medicine
•Cost $800 million – 1 billion dollars (US)
•Likelihood of success: 10%
6. Reasons for Failure in Development
Toxicity (22%)
Lack of Efficacy (31%)
Market Reasons (6%)
Poor Biopharmaceutical (PK) Properties (41%)
7. •From 1898 through to 1910 heroin was marketed as a non-addictive morphine
substitute and cough medicine for children. Bayer marketed heroin as a cure for
morphine addiction
•Heroin is converted to morphine when metabolized in the liver
8.
9. 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.
10. 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
11. 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
12. PROLONGATION OF DRUG ACTION
By prolonging absorption from the site of action –
Oral and parenteral (LORELIN DEPOT)
By increasing plasma protein binding
(OXALIPLATIN MEDAC)
By retarding rate of metabolism
(LIPAD)
(LIPOPLATIN)
(HAMSYL)
By retarding renal excretion
(CONTRARY TO DISODIUM PAMIDRONATE)
13. Ideal PK Properties of a Drug
• Must be efficacious with once/day dosing
(EXCEPT THROMBOMAX)
• One or two dose levels should be safe and
efficacious in all individuals
• No dosing adjustments should be required
with multiple dosing.
From a Marketing Perspective
14. Ideal PK Properties of a Drug
• Should give consistent plasma concentrations in all
individuals (patients) from one dose.
• No variability in metabolism
• Excretion by both renal and hepatic mechanisms for
those with liver or kidney problems
• Rapid, predictable onset of action
• Clearance high enough so compound is removed from
body if any untoward side-effects are observed.
• No accumulation
• No interaction with co-administered drugs due to
• High Protein Binding
• Metabolism (induction or inhibition)
• Interference with Excretion
From a Clinical Perspective
15. Products PK Property Indication
Oxaliplatin
High Plasma Protein Binding and
(MHRA certificate)
Decreased Frequency and
Approved efficacy
Pamidronate
Disodium Preparation (MHRA
Certificate)
Rapid excretion and low
adverse effect and dose
adjustments
Lorelin Depot Formulation
Decreased absorption and
delay frequency
Lipoplatin Peg-Liposomal Formulation
Decreased Metabolism,
Elimination and increased
half life. Results in Increase
Effectiveness and decreased
ADRs.
Lipad Peg-Liposomal Formulation As Above.
Hamsyl Pegylated Formulation
Delayed dosing and increase
effectiveness
Amgofil Recombinant Human Low Toxicity
Thrombomax As Above As Above
Weaponry of AMGOMED
