INTRODUCTION CLINICAL PHARMACOKINETICS Dr. Mohd B. Makmor Bakry, Ph.D., R.Ph. Senior Lecturer in Clinical Pharmacy Intensive Care Preceptor Faculty of Pharmacy Universiti Kebangsaan Malaysia

DEFINITION Pharmacology Pharmacodynamics Pharmacokinetics Drug’s mechanism of action, indications, side effects, interactions and ADME Pharmacodynamics Drug-receptor activity, effects of drug to the body Pharmacokinetics ADME, kinetic orders, rates, concentration vs time profile. Pharmacotherapeutics Use of pharmacologic agents to manage patient specific problems/diagnosis.

WHAT IS CLINICAL PHARMACOKINETICS? Concern about ADME, how to adjust the dosage regimen to suit the patient’s ADME characteristics and concentration vs time profile following the therapeutic planning. The service known as Therapeutic Drug Monitoring (TDM) or Clinical Pharmacokinetic Services

WHAT TO THINK FOR? Why patient is individualized? What affects drug absorption? What affects drug distribution? What affects drug metabolism? What affects drug excretion?

SPECIFIC DRUG PHARMACOKINETICS Indication(s) Common and important side effects Pharmacokinetics profile Initiating and adjustment of therapy regimen Monitoring therapeutic effects and side effects

After completion of the course, student should be able to: Rationalized the indication of the drug. Initiate drug regimen for the individual patient. Take useful blood sample for analysis and interpretation. Adjust the therapy regimen to suit the patient individual needs. Monitor the disease progression and drug side effects.

BACKGROUND KNOWLEDGE Physiology Pharmacology Pathology Normal organs function eg. the gut, the liver and kidney. Pharmacology Indication(s) of drug, drugs characteristics eg. absorption, distribution, metabolism and elimination, drug interactions. Pathology Pathophysiologic conditions eg. electrolytes imbalance, acid-base abnormalities, liver or kidney impairment. Biopharmaceutics Dosage form characteristics and route of administration.

THE PHASES 1 2 3 A D E M PHARMACOKINETICS Tablet (Q*) Q*-Receptor BIOPHARMACEUTICS PHARMACODYNAMICS A mucosal D blood Tablet (Q*) GIT Q*-Receptor tissue E kidney/liver M liver Elimination Metabolite

PHARMACOKINETIC PROCESSES Absorption Bioavailability (F) The percentage of the administered dose that reaches the systemic circulation. Absorption Rate (Ka) The speed of input into the systemic circulation. Distribution Volume of Distribution (Vd) The apparent volume into which the drug distributes within the body. Protein Binding The percentage of drug binds to the plasma protein.

PHARMACOKINETIC PROCESSES (CONT’) Elimination Clearance (CL) The volume of drug cleared per unit time. Elimination Rate Constant (Ke) The proportion of drug in the body eliminated per unit time. Elimination Half-life (t½) The time taken for the concentration to fall to half the previous value.

CONCENTRATION VS TIME PROFILE (Oral Administration) Cp A+D D+E Ke Ka A E Ke t

CONCENTRATION VS TIME PROFILE (Parenteral Administration) Cp D+E Ke Ke E t

CONCENTRATION VS TIME PROFILE (Continuous Infusion) Cp Input = output Input > Output t

CONCENTRATION VS TIME PROFILE (AUC, Cmax, tmax) Cp Cmax AUC t tmax

CONCENTRATION VS TIME PROFILE (Formulation, onset, duration of action) Cp Rapid absorbing Slow absorbing Sustained-release Therapeutic Range t

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