Pharmacokinetics Flashcards
4 main parts to pharmacokinetics
Absorption, distribution, metabolism, elimination
absorption
the proportion of an administered drug that reaches systemic circulation- bioavailability
what affect absorption (3)
GI, Route of admin and lipophilicity
GI AND ABSORPTION
contains proteases which may breakdown the drug, monoclonal antibodies- breakdown and recombinant proteins
- first pass metabolism - since hepatic vein takes blood from the stomach to the kidney
route of administration and absorption
IV= direct= 100% bioavailaiblity
Oral- via GI- we’ll tolerated but lower bioavailiablity
IM- slower, via capillary
Respiratory- across plasma men- rapid
drugs have to be
lipid soluble to pass membrane - therefor NOT IONISED
weak acids have
a low Ka, but a high pKA- pH at which 50% of the drug is ionised and 50% is nonionised
Distribution is referred to as
the volume of distribution
the volume of distribution
Vd
what is Vd
process by which drug is transferred from the blood to the tissue
- after absorption the drug equilibrates between the plasma and tissue
more detailed definition of Vd
‘vd represents the volume in which total amount of drug would need to be dissolved to match plasma conc’
what affects Vd
- drug size
- lipophilicity
- body composition
Vd=
Dosage/ conc of drug in plasma
Vd unit
mL
High plasma conc=
low Vd- drug not widely distributed
Low plasma conc=
high Vd - drug widely distributed
metabolism occurs in
the cell e.g. prodrug and in the liver = first pass metabolism
first pass metabolism
reduces bioavailability
- most drugs are metabolised slightly but the gut or the liver
- occurs in the LIVER and deactivates drugs
if first pass metabolism occurs
higher dose may occur
bioavailability is 100% if given via
IV
hepatic clearance
metabolism by the liver
renal clearance
exertion by the kidney
zero order drugs
constant AMOUNT of drug cleared per unit of time
first order drugs
constant PROPORTION of drug cleared per unit time
most drugs are
FIRST ORDER
what does zero order graph look like
straight decrease over time
what does first order graph look like
exponential decrease over time
2nd order drugs
4x rate of clearance
3rd order drugs
8 x rate of clearance
how is renal clearance measured
experimentally following IV admin of known out of drug
Renal clearance =
[drug] in urine time flow rate/ [drug] conc in plasma
factors effecting renal clearance
- renal blood flow
- drug lipophilicity
which drugs are most easily reabsorbed in the kidneys
WEAK ACIDS since they are more lipid soluble- have a lower Ka and higher pKa
low pH in urine=
less excretion
plasma half life
the time in which plasma conc reaches by half
plasma half life for first order
exponential decrease
plasma half life for zero order
increased - straight line
how to measure plasma half life
measured experimentally following IV admin of known amount t of drug
a drug with a short half life
may require regular repeats
drug targeting is good because
1) reduces side effect
2) increases bioavailability
3) more predictable response
4) less of the drug needed
targeting drugs exploits
property of target tissue e.g. pH
IC50
conc of antagonist that reduces the biological effect of an agonist by 50%
