Pharmacokinetics Flashcards
Define pharmacokinetics
The measurement and formal interpretation of changes with time of drug concentrations in one or more different regions of the body in relation to dosing
Pharmacokinetics describes what the body does to the drug. This encompasses its abdorption, distribution, metabolism and elimination
Understanding PK profiles of drugs allows us to:
Develop drugs Decide on appropriate dosages Determine dosing regimens Interpret drug interactions Adjust doses according to response
Define clearance
Clearance is expressed as volume over time, eg mL/min
It is defined as the **volume of blood cleared irreversibly of drug, per unit of time
Pharmacokinetic parameter that describes drug elimination
Important for maintenance dosing
Volume of plasma which contains the total amount of drug removed from the body in unit of time
Drug clearance can be determined in an individual patient by measuring plasma concentration of drug until steady state is achieved
Renal Clearance
Net effect of:
Glomerular filtration Active secretion and Passive reabsorption
Only unbound drug is filtered at the glomerulus
Glomerular filtration rate is assumed to be 7.2L/hour for a healthy adult
Describe the volume of distribution
Vd is expressed as volume e.g. mL
It represents teh voleume in whcich the amount of drug in the body would need to be uniformly distributed to produce the observed concentrations in the blood.
It is not a real volume
Indicates accumulation of drugs in tissue compartments
- A drug with a low Vd is mostly water soluble and will stay predominantly in the plasma (ie would not distribute into other sites like adipose tissue)
- A drug with a large Vd is more likley to move outside of the circulation and bind to other sites (like adipose tissue).
*The larger the Vd the more widespread the drug is within the body
Define half-life
Half-life is expressed as time e.g. hours.
Is calculated as 0.693* Vd / Cl*
It is defined as the time taken for blood/plasma drug conentration to fall by one half
Half life will not change with variations in dose for drugs that follow ‘first-order’ kinetics
Can be used to determine the duration of action of a drug after a single dose
It takes 3-5 half-lives to reach steady state (with constant dosing)
Describe the area under the curve
It represents the constant plasma conecntration i.e. - when rate of drug administration is equal to rate of drug elimination.
It is expressed as concentration and time
Describe steady state (Css)
Css is expressed as concentration or mg/L.
It describes the concentration of drug in systemic circulation as a function of time post dose
Describe zero-order kinetics
Elimination rate does not increase in proportion to dose and concentration
Describe first order kinetics
Constant proportion of drug is eliminated per unit of time
Describe the loading dose
It is defined as the inital amount of drug required to reach the target concentration.
It is calculated using Vd.
Loading dose = Vd x target peak concentration or Cp
Describe maximum concentration or Cmax
it is the maximum concentration of the drug, following administration
Describe the time to maximum concentration or Tmax
The time taken to reach Cmax
Describe maintenance dose
Dose required to maintain target plasma concentration at steady state.
It is calculated by multiplting steady state conecentratuon by clearnace. Expressed as mg
List routes of administration
- oral or rectal
- percutaneous
- intravemous
- inhalation
- intrathecal
- IV
- IM
End up in plasma.
If oral –> gut –> plasma but also liver (kidney, urine elimination) - feces direct elimination
IV–> plasma-> breast and seat glands
other routes can end up metabolising drug e.g. IT/CSF end up in plamsa, metabolised by liver etc
Describe absorption, mechanisms of absorption, and variables that affect absorption
Before a drug can be distributed to its site of action it must be absorbed
Drugs need to be able to cross biological membrane(s) to reach systemic circulation.
Lipid soluble drugs readily pass through lipid membranes Ionised drugs have difficulty crossing cell membranes Aquaporins in cell membranes allow the passage of small uncharged water soluble substances
Passive diffusion and carrier-mediated transport allow movement of drugs through the body
Passive diffusion - molecules travel down concentration gradient. This is the most common form of transport and is influenced by: surface area of membrane exposed to drug, concentration gradient of drug, lipophilicity of drug, ionisation state of drug
Carrier-mediated transport - Requires the involvement of membrane protein for the movement of a drug across a biological membrane. Can be ACTIVE (requires energy) or FACILITATED (not requiring energy)
Active transport: Permits movement of a compound against a concentration gradient or electrochemical gradient.
Variables:
Blood flow
Rich blood supply enhances absorption
Solubility
A drug must be in solution to be absorbed
Ionisation
Many drugs are weak acids or bases
Ionised form does not diffuse readily through cell membranes; unionised form is usually more lipid soluble and more capable of crossing cell membranes (Extent of ionisation is dependent on the pH of the environment)
Formulation
Drug formulations can be manipulated to achieve desirable absorption characteristics (eg slow release or enteric formulations)
Route of administration can affect both onset and magnitude of drug action.
A drug can enter systemic circulation by being injected there (IV) or absorbed from extravascular sites
Describe oral absorptio
Most common route of admin for drugs
Safe, convenient and economical
Can be absorbed from the
Oral cavity (sublingual or buccal administration)
Stomach (noting the high pH in this environment)
Small intestine (major site of absorption of orally administered drugs and pH is close to neutral)
Rectal (can be used for local or systemic effects)
