JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD

Course Objective

This course is designed to enable students to understand the basics principles

and applications of pharmacokinetics in designing the individualized dosage regimen, to interpret the plasma drug concentration profile in altered pharmacokinetics, drug interactions and in therapeutic drug monitoring processes to optimize the drug dosage regimen. Also, it enables students to understand the basic concepts of pharmacogenetics, pharmacometrics for modeling and simulation of in kinetic data.

Course Outcome

Upon completion of this course it is expected that students shall be able to:

• Design the drug dosage regimen for individual patients
• Interpret and correlate the plasma drug concentrations with patients' therapeutic outcomes Recommend dosage adjustment for patients with renal/ hepatic impairment Recommend dosage adjustment for pediatrics and geriatrics
• Manage pharmacokinetic drug interactions
• Apply pharmacokinetic parameters in clinical settings
• Interpret the impact of genetic polymorphisms of individuals on pharmacokinetics and or pharmacodynamics of drugs
• Do pharmacokinetic modeling for the given data using the principles of pharmacometrics

UNIT - I

Introduction to Clinical Pharmacokinetics: Compartmental and Non-compartmental models, Renal and non-renal clearance, Organ extraction and models of hepatic clearance, Estimation and determinants of bioavailability, Multiple dosing, Calculation of loading and maintenance doses. Designing of dosage regimens: Determination of dose and dosing intervals, Conversion from intravenous to oral dosing, Nomograms and Tabulations in designing dosage regimen.

UNIT - II

Pharmacokinetics of Drug Interactions: Pharmacokinetic drug interactions, Inhibition and Induction of Drug metabolism, Inhibition of Biliary Excretion. Pharmacogenetics: Genetic polymorphism in Drug metabolism: Cytochrome P-450 Isoenzymes, Genetic Polymorphism in Drug Transport and Drug Targets, Pharmacogenetics and Pharmacokinetic/ Pharmacodynamic considerations. Introduction to Pharmacometrics: Introduction to Bayesian Theory, Adaptive method or Dosing with feedback, Analysis of Population pharmacokinetic Data.

UNIT - III

Non-Linear Mixed Effects Modelling: The Structural or Base Model, Modeling Random Effects, Modeling Covariate Relationships, Mixture Model, Estimation Methods, Model Building Techniques, Covariate Screening Methods, Testing the model assumptions, Precision of the parameter estimates and confidence intervals, Model misspecification and violation of the model assumptions, Model Validation, Simulation of dosing regimens and dosing recommendations, Pharmacometrics software.

UNIT - IV

Altered Pharmacokinetics: Drug dosing in the elderly, Drug dosing in the pediatrics, Drug dosing in the obese patients, Drug dosing in the pregnancy and lactation, Drug dosing in the renal failure and extracorporeal removal of drugs, Drug dosing in the in hepatic failure.

UNIT - V

Therapeutic Drug Monitoring: Introduction, Individualization of drug dosage regimen (Variability – Genetic, age, weight, disease and Interacting drugs), Indications for TDM, Protocol for TDM, Pharmacokinetic/Pharmacodynamic Correlation in drug therapy. TDM of drugs used in the following conditions: Cardiovascular disease: Digoxin, Lidocaine, Amiodarone; Seizure disorders: Phenytoin, Carbamazepine, Sodium Valproate; Psychiatric conditions: Lithium, Fluoxetine, Amitriptyline; Organ transplantations: Cyclosporine; Cytotoxic Agents: Methotrexate, 5-FU, Cisplatin; Antibiotics: Vancomycin, Gentamicin, Meropenem.

REFERENCE BOOKS:

• 1. Leon Shargel, Susanna Wu-Pong, Andrew Yu. Applied Biopharmaceutics & Pharmacokinetics. New York: McGraw Hill.
• 2. Peter L. Bonate. Pharmacokinetic - Pharmacodynamic Modeling and Simulation. Springer Publications.
• 3. Michael E. Burton, Leslie M. Shaw, Jerome J. Schentag, William E. Evans. Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring. Iippincott Williams & Wilkins.
• 4. Steven How-Yan Wong, Irving Sunshine. Handbook of Analytical Therapeutic Drug Monitoring and Toxicology. CRC Press, USA.
• 5. Soraya Dhillon, Andrzej Kostrzewski. Clinical pharmacokinetics. 1st edition. London: Pharmaceutical Press.
• 6. Joseph T. Dipiro, William J. Spruill, William E. Wade, Robert A. Blouin and Jane M. Pruemer Concepts in Clinical Pharmacokinetics. American Society of Health-System Pharmacists, USA.
• 7. Malcolm Rowland, Thomas N. Tozer. Clinical Pharmacokinetics and pharmacodynamics: concepts and applications. Iippincott Williams &Wilkins, USA.
• 8. Evans, Schentag, Jusko. Applied pharmacokinetics. American Society of Health system Pharmacists, USA.
• 9. Michael E. Winter. Basic Clinical Pharmacokinetics. Iippincott Williams &Wilkins, USA.
• 10. Milo Gibaldi. Biopharmaceutics and Clinical Pharmacokinetics. Pharma Book Syndicate, USA.
• 11. Dhillon and Kostrzewski. Clinical pharmacokinetics. Pharmaceutical Press, London.
• 12. John E. Murphy. Clinical Pharmacokinetics. 5th edition. US: American Society of Health- System Pharmacist, USA.
• 13. Relevant review articles from recent medical and pharmaceutical literature M. Pharm I Year II Sem (PHARMACY PRACTICE)