Drug Discovery & Clinical Evaluation of New Drugs

Dr. Keerthi Sagar J

Random ScreeningSerendipityMolecular

modificationRational drug

designingDesigning of a

Prodrug

Blind hitting procedure

Studies on animal behavior etc.

Eg: Morphine, Atropine, Digitalis, Penicillin

Limitations: Cumbersome , Time consuming, Expensive, Might not have fruitful results

Methods of Drug Development

Random ScreeningSerendipityMolecular

modificationRational drug

designingDesigning of a

Prodrug

Happy observation by chance

New use of old drugSide effects find a

new therapeutic useEg: Lignocaine,

Phenytoin, Methotrexate, Cyclophosphamide, Minodoxil

Methods of Drug Development

Random ScreeningSerendipityMolecular

modificationRational drug

designingDesigning of a

Prodrug

Synthesis of chemical analogues of drugs

Advantage in pharmacokinetic parameters

Decrease toxicityEg: ThaizidesLimitations: Me too

Drugs

Methods of Drug Development

Random ScreeningSerendipityMolecular

modificationRational drug

designingDesigning of a

Prodrug

Understanding biological activity and chemical structure

Eg: ACE inhibitors, H2 Antagonists

Methods of Drug Development

Random ScreeningSerendipityMolecular

modificationRational drug

designingDesigning of a

Prodrug

Eg: Levodopa, Paracetamol, N- acetyl Procainamide

Methods of Drug Development

From Hits To Leads

Sochlet Apparatus

Analysis of Active IngredientGas ChromatographyUV SpectrophotometerHPLCHPTLCNMR SpectrophotometerX- Ray Crystallography

Invitro methods Bioassay

Direct end point assayQuantal assay Graded assay

a. Bracketing assayb. Matching assayc. Interpolation assayd. Multiple point assay

In vivo studiesAnimal studies for behavior

Eddy’s Hot PlateElevated plus mazeRota rod apparatusElectroconvulsiometer

Toxicity studiesAcute toxicitySubacute toxicityChronic toxicitySpecial toxicity

Male fertility studiesFemale fertility studiesTeratogenicityCarcinogenicity

Clinical trialsSchedule Y – Drugs & Cosmetics Rules 2005

[Ministry of Health & Family Welfare]Definition : A systematic study of a new drug

in human subjects to generate data for discovering and verifying the clinical, pharmacological & adverse effects with the objective of determining safety and efficacy of new drugs

Need for clinical trialsEvaluation of new drugs for its efficacy &

safetyTo know benefits and risks

Types of Clinical trialsTherapeutic trials

Analgesics, anticonvulsantsPrevention trials

Vitamins, VaccinesDiagnostic trials

Finding better testScreening trials

MRI, PET ScanQuality of life trials

Side effects reducing drugs

Requirements for Clinical TrialsPreclinical study dataClearance from IRB/ IECInformed ConsentApproval from Regulatory authorities like

FDA, IND

Informed consentOral consentWritten consent

Institutional Ethics Committee