CHAPTER 3:
PHARMACOKINETICS
22nd October 2021
INTRODUCTION:
Pharmacokinetics denotes the effects of biologic systems on drugs
The major processes involved in pharmacokinetics are
o
o absorption o metabolism
o distribution o elimination
Pharmacokinetic data are essential to calculate the “loading” and “maintenance” doses
HIGH-YIELD TERMS TO LEARN:
Volume of Distribution (V d ):
amount of drug in body
V d=
drug concentration in plasma or blood
Clearance (CL):
rate of elimination of drug
CL=
plasma drug concentration
Half-Life: period of time in which the drug concentration in body / blood drops by 50%
Bioavailability: the fraction / percentage of administered drug that reaches the
systemic circulation (i.e., bioavailability in case of IV administration = 100%)
Area Under the Curve (AUC): the area under the drug concentration – time curve
Peak and Trough Concentration: maximum and minimum drug concentration
achieved during repeated dosing cycle
Minimum Effective Concentration: plasma drug concentration bellow which a
patient’s response is too small for clinical benefit
First-pass effect, presystemic elimination: elimination of drug that occurs after
administration but before it enters the systemic circulation (e.g., during passage
through gut wall, portal circulation or liver when drug is taken orally)
Steady State: the condition in which the average total amount of drug in the body does
not change over multiple dosing cycle (i.e., rate of elimination = rate of administration)
Biodisposition: synonym for pharmacokinetics (absorption, distribution, metabolism,
elimination)
, EFFECTIVE DRUG CONCENTRATION:
The concentration of the drug (DC) at the receptor site is called EDC
The plasma concentration is a function of:
o Rate of drug input
o Rate of elimination
o Rate of distribution
If the rate of input is known, the remaining processes are described by:
o Apparent Volume of Distribution (V d )
o Clearance (CL)
VOLUME OF DISTRIBUTION:
amount of drug in body
V d=
drug concentration in plasma or blood
Denoted as apparent V d
V d is sometimes expressed as V d /kg
Liver disease can alter the V d for drugs that bind to plasma proteins (e.g., albumin)
The V d may:
o greatly exceed the total body volume
e.g., Quinacrine: 50,000 L/V d in a person whose body volume is 70 L
o greatly fall to a small portion of the body volume
e.g., if a drug is completely retained in the plasma
CLEARANCE:
rate of elimination of drug
CL=
plasma drug concentration
First-Order Kinetics: is a concentration-dependent process (i.e., the higher the
concentration, the faster the clearance)
For a drug eliminated with first order kinetics, clearance is a constant.
clearance is sometimes expressed as CL/Kg
Clearance depends on
o the drug
o the blood flow
o the condition of the organs of elimination in the patient
2
PHARMACOKINETICS
22nd October 2021
INTRODUCTION:
Pharmacokinetics denotes the effects of biologic systems on drugs
The major processes involved in pharmacokinetics are
o
o absorption o metabolism
o distribution o elimination
Pharmacokinetic data are essential to calculate the “loading” and “maintenance” doses
HIGH-YIELD TERMS TO LEARN:
Volume of Distribution (V d ):
amount of drug in body
V d=
drug concentration in plasma or blood
Clearance (CL):
rate of elimination of drug
CL=
plasma drug concentration
Half-Life: period of time in which the drug concentration in body / blood drops by 50%
Bioavailability: the fraction / percentage of administered drug that reaches the
systemic circulation (i.e., bioavailability in case of IV administration = 100%)
Area Under the Curve (AUC): the area under the drug concentration – time curve
Peak and Trough Concentration: maximum and minimum drug concentration
achieved during repeated dosing cycle
Minimum Effective Concentration: plasma drug concentration bellow which a
patient’s response is too small for clinical benefit
First-pass effect, presystemic elimination: elimination of drug that occurs after
administration but before it enters the systemic circulation (e.g., during passage
through gut wall, portal circulation or liver when drug is taken orally)
Steady State: the condition in which the average total amount of drug in the body does
not change over multiple dosing cycle (i.e., rate of elimination = rate of administration)
Biodisposition: synonym for pharmacokinetics (absorption, distribution, metabolism,
elimination)
, EFFECTIVE DRUG CONCENTRATION:
The concentration of the drug (DC) at the receptor site is called EDC
The plasma concentration is a function of:
o Rate of drug input
o Rate of elimination
o Rate of distribution
If the rate of input is known, the remaining processes are described by:
o Apparent Volume of Distribution (V d )
o Clearance (CL)
VOLUME OF DISTRIBUTION:
amount of drug in body
V d=
drug concentration in plasma or blood
Denoted as apparent V d
V d is sometimes expressed as V d /kg
Liver disease can alter the V d for drugs that bind to plasma proteins (e.g., albumin)
The V d may:
o greatly exceed the total body volume
e.g., Quinacrine: 50,000 L/V d in a person whose body volume is 70 L
o greatly fall to a small portion of the body volume
e.g., if a drug is completely retained in the plasma
CLEARANCE:
rate of elimination of drug
CL=
plasma drug concentration
First-Order Kinetics: is a concentration-dependent process (i.e., the higher the
concentration, the faster the clearance)
For a drug eliminated with first order kinetics, clearance is a constant.
clearance is sometimes expressed as CL/Kg
Clearance depends on
o the drug
o the blood flow
o the condition of the organs of elimination in the patient
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