Summary principles of oharmacokinetics

Principles of pharmacokinetics

PK) Pharmacokinetics: how the body affects the drug
- All the blood from the small intestine will end up in the liver
- Fate of drug in the body
 Description of processes
 Mechanisms of processes
 Time profiles of concentrations
 Quantitative approach – mathematical functions

Why pharmacokinetics?
- Aid for assessment of the right dose for the individual patients
 Amount, dosing, interval, duration
- To achieve an optimal therapeutic effect: optimal balance between the desired effect
and the risk of adverse effects and toxicity.
- To understand the relationship between dose and effect. You want to know what is
ending up in the plasma, the exposure.
- Fate of administered drug in the body
 Distribution to organs, tissues, cells
 Formation of metabolites
 Excretion of parent/metabolites
 Accumulation in the body
 Damage to foetus
 Excretion into milk

PD) Pharmacodynamics: how the drug affects the body

Therapeutic window
- The range of drug dosages which can treat disease effectively without having toxic
effects
- Every drug sold in the trekpleister/etos/etc has a wide therapeutic window
- A drug for instance for cancer has a narrow therapeutic window and needs to be
prescribed.
- Upper limit: risk of side-effects/toxicity. Maximal desired effect
- Lower limit: minimal desired effect

Dose calculation
Calculation to make sure you’re in the therapeutic window and have the therapeutic effect.
Desired plasma concentration profile  dose / dosing interval

TDM) therapeutic drug monitoring
- Only metabolized drugs are measured
- the measurement of specific drugs and/or their breakdown products (metabolites) at
timed intervals to maintain a relatively constant concentration of the medication in the
blood
- Focusses on drugs with a narrow therapeutic window (liver transport)

, - Desired plasma concentration + measured plasma concentration  dose / dosing
interval



Dosing Plasma concentration Effect
Dose amount Time profile Intensity
Dosing Minimum – maximum Risk of adverse
interval effects and toxicity
Average level
exposure



Most drugs are lipophilic. (permeable for membranes)
Free fraction: parameter that indicates how much drug is not bound in blood.
Plasma half-life: how fast is the drug eliminated from plasma.
Speed of onset: how fast do I think that this drug will work?

A absorption from site of administration to systemic circulation
D distribution to various tissues, including target site
M metabolism biotransformation to metabolites
- Enzymatic reactions / metabolites / enzyme induction / enzyme inhibition /
pharmacogenetics – polymorphism.
E excretion urine, bile → feces
- Urine / feces / sweat / bile / vapor / milk

Free (unbound to a carrier protein) drug counts, these drugs will be
excreted.

Route of administration
- Intravascular (directly into bloodstream): bolus/infusion
- Extravascular (absorption required for systemic effect):
intramuscular/oral/subcutaneous/rectal
- Local (not aiming at systemic effect): skin/lungs/epidural

Enterohepatic cycle
reuptake of substance from the intestine after its excretion via bile produced
by the liver.
- uptake from portal vein into liver
- excretion into bile
 parent compound or metabolite
- bile via gall bladder into intestinal lumen
 (metabolite may be transformed into parent compound)
- uptake from intestinal lumen into blood
 (re-)absorption
- via portal vein to liver