CLINICAL

PHARMACOLOGY
(Pharmacotherapeutics)
 CLINICAL
PHARMACOLOGY
• Also known as
pharmacotherapeutics, it is a branch
of medical sciences which is most
concerned with rational development
of drugs, effective and safe use of
drugs (RDU or RUD).
• Proper evaluation of drugs and other
chemical entities in humans for the
diagnosis, prevention, alleviation,
and cure of disease and disease
 CLINICAL
PHARMACOLOGY
• Simple blind trials
– Physician and associates – but not the
patient – know the substance being used.

• Double blind trials

– Neither the individual administering the
compound nor the patient knows the
identity of the substance. All the
materials are coded including the test
substance and a placebo and, if possible,
an already known active substance
therapeutically similar to the one being
tested (standard reference of positive
 DEVELOPMENT OF NEW
•
DRUG
Animal study  human study.
• Human dose – Initial single human dose would be a
fraction of a minimum effective dose in animal study.
Example: Minimum effective dose is 10 mg.
– If rat is the test animal – human dose is 1/200 of 10 mg.
– If dog is the test animal – human dose in 1/10 of 10 mg.
– Monkeys or orangutans and baboons – human dose is ½
of MED.
• Dose is gradually increased until a response appears
or until a maximum tolerated dose is established
(dose which does not elicit undesirable effects).
• No individual should be exposed to more than a
single dose in a short period of time – preventing
cumulative effect.
• Minimum effective dose based on dose-
response relationship
 NEW DRUG DEV’T. AND APPROVAL
PROCESS
New chemical entity: Sources, drug
synthesis, molecular modification,
isolation from plants
Pre-clinical Studies: Chemistry, physical properties,
biological pharmacology, toxicology, pre-formulation

Investigational New Drug

Application (IND): Submission,
FDA Review
Pre-clinical Studies continued +
Clinical
long-term animal toxicity,
Trials:
product formulation,
Phases I, II,
manufacturing and controls,
III
New Drug Applicationpackage
(NDA):and label design
Submission, FDA Review, Pre-
approval plant inspection, FDA
Action
Post-marketing: Phase IV clinical studies,
clinical pharmacology/toxicology, additional
indications/ADR reporting, product defect
CLINICAL TRIALS IN DEVELOPING A
NEW DRUG IN HUMANS
• 2-3 years Phase I Measurement of
pharmacologic action, potency,
side effects
(pharmacodynamics), pharmacokinetics
usually in normal, healthy volunteers
done by clinical pharmacologists in
research setting.
• 1-2 years Phase II
– Early: Selection of few patients with disease
syndrome. Determination of drug
efficacy and dosage ranges. Special
toxicity studies if indicated.
– Late: Large number of clinical patients.
Longer periods of therapy.
CLINICAL TRIALS IN DEVELOPING A
NEW DRUG IN HUMANS
• 1-2 years Phase III Large scale comparative trials
in patients. Designed to establish
efficacy. Compare the new drug with other
available treatments. Establish optimal
dosage. Determine incidence of ADR before drug
is licensed for marketing. Set up blind or
double-blind study with randomized
selection of patients and controls. Dosage
forms and routes of administration clearly
defined.
• 1-3 years Phase IV Approval of NDA by FDA for
marketing. Surveillance of the safety and
efficacy of the drug by the manufacturer
who reports periodically to the FDA. Drug
may be withdrawn if unexpected undue toxicity
becomes evident. Drug may be released only
for a limited use in selected patients under