The document provides an introduction to clinical pharmacokinetics, detailing the processes of drug absorption, distribution, metabolism, and excretion. It emphasizes the importance of understanding linear and nonlinear pharmacokinetics in optimizing dosage regimens and minimizing adverse effects. Key concepts include steady state concentrations and their relationship with dosage adjustments, illustrating how some drugs may follow saturable or Michaelis-Menten pharmacokinetics.

1. UNIT:1
INTRODUCTION TO CLINICAL
PHARMACOKINETICS
LECTURE SPEAKER
Dr. S P Srinivas Nayak.,
PharmD.,RPh.,MSc.,(PhD)

2. LECTURE OBJECTIVES
After completion of this lecture, student will be able to:
• Explain clinical pharmacokinetics
• Discuss linear and non linear pharmacokinetics
• Describe steady state concentration

3. INTRODUCTION
Pharmacokinetics is the study of
• Absorption
• Distribution
• Metabolism
• Excretion of drugs

4. Introduction
• When drugs are given extravascularly (e.g., orally,
intramuscularly, applied to the skin via a transdermal patch,
etc.), absorption must take place for the drug molecules to
reach the systemic circulation

5. Introduction
• In order to be absorbed, the drug molecules must pass
through several physiological barriers before reaching the
vascular system
• For example, when a medication is given orally, the drug
dosage form must release drug molecules via dissolution
• These molecules must pass through the various layers of the
gastrointestinal tract where they enter capillaries

6. Introduction
• Distribution occurs when drug molecules that have entered
the vascular system pass from the bloodstream into various
tissues and organs such as the muscle or heart
• Metabolism is the chemical conversion of the drug molecule,
usually by an enzymatically mediated reaction, into another
chemical entity referred to as a metabolite

7. • The metabolite may have the same, or different,
pharmacological effect as the parent drug, or even cause toxic
side effects
• Excretion is the irreversible removal of drug from the body
and commonly occurs via the kidney or biliary tract

8. Definition
• “Clinical pharmacokinetics is the discipline that applies
pharmacokinetic concepts and principles in humans in order
to design individualized dosage regimens which optimize the
therapeutic response of a medication while minimizing the
chance of an adverse drug reaction”

9. • Pharmacodynamics is the relationship between drug
concentration and pharmacological response
• It is extremely important for us to realize that the change in
drug effect is usually not proportional to the change in drug
dose or concentration

10. Example
• For example, the increase in pharmacological effect is greater
when the initial concentration is low compared to the change
in drug effect observed when the initial concentration is high

11. Reason
• The reason that most drugs follow this pattern is because
their pharmacological effect is produced by forming a
complex with a drug receptor
• Once the drug-receptor complex is formed, the
pharmacological effect is expressed
• In clinical situations, patients may need to tolerate some side
effects in order to obtain the maximal pharmacological effect
of the agent

12. Linear Versus Nonlinear
Pharmacokinetics
• When medications are given on a continuous basis, serum
concentrations increase until the rate of drug administration
equals the elimination rate
• For the intravenous infusion, serum concentrations increase
in a smooth pattern until steady state is achieved

13. Linear Versus Nonlinear
Pharmacokinetics

14. • During oral dosing, the serum concentrations oscillate around
the intravenous profile
• This increases during drug absorption and decreases after
absorption is complete and elimination takes place
• This equilibrium condition is known as steady state and is
extremely important in clinical pharmacokinetics because
usually steady-state serum or blood concentrations are used to
assess patient response and compute new dosage regimens

15. • If a plot of steady state concentration versus dose yields a
straight line, the drug is said to follow linear pharmacokinetics
• In this situation, steady-state serum concentrations increase or
decrease proportionally with dose
• Therefore, if a patient has a steady-state drug concentration of
10 μg/mL at a dosage rate of 100 mg/h, the steady-state
serum concentration will increase to 15 μg/mL if the dosage
rate is increased to 150 mg/h

16. Non-linear Pharmacokinetics
• When steady-state concentrations change in a disproportionate
fashion after the dose is altered, a plot of steady-state
concentration versus dose is not a straight line and the drug is
said to follow nonlinear pharmacokinetics
• When steady-state concentrations increase more than expected
after a dosage increase, the most likely explanation is that the
processes removing the drug from the body have become
saturated

17. Saturable or Michaelis-Menten
Pharmacokinetics
• This phenomenon is known as saturable or Michaelis-Menten
pharmacokinetics
• Both phenytoin and salicylic acid follow Michaelis-Menten
pharmacokinetics
• When steady-state concentrations increase less than expected
after a dosage increase, there are two typical explanations

18. Saturable or Michaelis-Menten
Pharmacokinetics
• Some drugs, such as valproic acid and disopyramide, saturate
plasma protein binding sites so that as the dosage is increased
steady-state serum concentrations increase less than
expected
• Other drugs, such as carbamazepine, increase their own rate
of metabolism from the body

19. Autoinduction
• This process is known as autoinduction of drug metabolism
• In either case, the relationship between steady-state
concentration and dose for drugs that follow nonlinear
pharmacokinetics
• Drugs that exhibit nonlinear pharmacokinetics are oftentimes
very difficult to dose correctly

20. Autoinduction

21. Example
Dose
CURACILLIN STEADY-STATE
CONCENTRATIONS (mg/L)
BETTERMYCIN STEADY-
STATE CONCENTRATIONS
(mg/L)
0 0 0
100 15 25
250 37.5 62.5
500 75 190
1000 150 510

22. Summary
• Clinical pharmacokinetics is application of pharmacokinetic
concepts and principles in humans in order to design
individualized dosage regimens
• If a plot of steady state concentration versus dose yields a
straight line, the drug is said to follow linear pharmacokinetics
• If a plot of steady-state concentration versus dose is not a
straight line and the drug is said to follow nonlinear
pharmacokinetics

23. Thank you… all the best