Pharmacokinetics Flashcards
What are the four basic parameters of pharmacokinetics?
Clearance, volume of distribution, bioavailability, half-life.
What is exposure and how does this fit into the time-concentration graph?
Exposure is the area under the concentration-time curve (AUC) typical units mgh/L.
Why is drug absorption not relevant for IV administration, but oral (po) is?
Because IV is injected straight into the bloodstream so it has 100% absorption, yet drugs administered by other roots undergo loss of drug before reaching the bloodstream where they are absorbed.
Define bioavailability:
The fraction of dose reaching the systemic circulation.
How is bioavailability calculated?
F= AUCpo/AUCiv x doseiv/dosepo. If the doses are the same then F= AUCpo/AUCiv.
What is a limitation of bioavailability?
First pass effect is the loss of drug occuring before the drug reaches the systemic circulation.
Describe distribution of the drug:
Processes involved in the delivery of the drug to the tissues via the arterial blood, in the transfer of the drug from the general circulation to tissues.
What is the parameter of distribution?
Volume of distribution.
How is volume distribution calculated?
V= amount of drug in the body/plasma drug concentration.
What are some determinants of volume of distribution?
Body mass, tissue binding (increased volume), drug binding to plasma elements (decreased volume).
Define the loading dose:
This is the first dose of drug treatment, and is required to achieve a target concentration rapidly. It is related (and depends on) volume distribution.
How is the loading dose calculated?
LD (mg) = V (L) x target concentration (mg/L)
If the V and target concentration are known then it is possible to work out the loading dose for a drug.
Define drug elimination:
Drug elimination is the irreversible removal of the drug from the body.
What are the two processes by which drug elimination can occur?
- Drug excretion- loss of drug in bile or urine for H2O soluble drugs.
- Drug metabolism- conversion of the drug into another chemical species for lipid soluble drugs.
What parameter defines drug elimination?
Clearance
Define clearance (CL):
Volume of plasma cleared of drug per unit time (L/h), a constant.
How can clearance be calculated?
Elimination rate (mg/h) = clearance (L/h) x concentration (mg/L)
CLtotal body= CLrenal + CLhepatic + CLother
CL=dose/AUC
Define maintenance dose rate (MD):
This is the dose rate to achieve and maintain a target concentration. At steady state, dose rate in=rate of elimination.
How can maintenance dose rate be calculated?
MD(mg/h)= CL(L/h) x target concentration(mg/L)
If CL and target concentration are known then it is possible to estimate the maintenance dose of a drug.
Define half life (T1/2):
Time required for drug concentration to fall by a half, and depends (independently) on volume and clearance. Usually constant irrespective of drug concentration. The amount of drug in the body at any time is related to the number of half-lives from drug administration.
What can half-life be used to estimate?
How much drug is left in the body and how long it will take to reach steady-state.
How can half life be calculated?
T1/2= 0.7 V/CL
How does half life relate to drug elimination?
After 1 half life, 50% of the drug will have been eliminated.
After 4 half lives, >90% of the drug will have been eliminated from the body.
How can elimination time be calculated?
Time required= 4 x half life length
