PK calaculations

• absorbed through the gastrointestinal tract

• go through portal blood supply and liver

• absorbed by active transport or passive diffusion

• unionised drug crosses membrane

• absorption rate constant

absorption

• proportion of extra-vascular dose absorbed into systemic circulation

bioavaliability

• by IV data

• for oral - F x dose

• apparent clearance - for the oral dose using oral bioavailability

true clearance

• lag time - time it takes for the dose to be absorbed

• ka should be higher or close to K line

difference in Ka and K line

• enzymes in the lumen which can metabolise the drug

• loss of drug in the liver

• higher this is - lower bioavaliability

• first pass loss - liver metabolism and intestinal metabolism

first pass loss

• tablet needs to broken up into smaller parts to be absorbed

• finer particles are absorbed faster

dosage form absorption

• two compartment model

• distribution in tissues

• central and peripheral compartment

• central - V1

• a - distribution and elimination

• b - elimination only

• C0 = A + B

• distribution into different tissues - is different

distribution of the drug

• unbound drug

• drug bound to proteins - unable to move out of the central compartment and the tissues

central compartment

• high MW and plasma conc

• reduce in liver disease

• weak acids, NSAIDs - bind to it

albumin

• the amount of drug which is unbound

• active concentration of the drug

• can increase where albumin is low

• volume of distribution can be larger than volume in the tissues - concentration in tissues is higher than conc in plasma

fraction un bound

• average time the molecules reside in the body

• time for 63.2% of dose to be eliminated

• model - independent parameter based on AUMC

MRT

• initial drug in the body at time zero

• calculated by IV

• smallest

V1

• volume of distribution at terminal phase ( when eliminating)

• largest volume

Vz

• volume distribution at steady state

Vss

• providing patient with enough medication to achieve a target concentration

loading dose

• peak concentrations and minimal concentrations are the same

• based on the expotential increase as a function of half-life

• 4-5 half lives to reach steady state

• time to reach steady state does not depend on the dose and dose interval

steady state

• not the arthimetic mean or geometric mean of Cssmin and Cssmax

• AUC/dose interval

• use IV values

• most accurate equation

Css av

• IV infusion

• syringe pump

• portable infuser

• transdermal delivery

• all systemic

• sustain/controlled release

• reaches steady state concentration - drops as stops infusion

• k - calculated by the infusion - post infusion values

• loading dose used to help reach target concentration

constant rate drug administration

• time course of drugs in the body

pharmcokinetics

• relationship between drug concentration at the site of action and the pharmcological effect

• free drug concentration travels to this area

• Emax - maximum effectiveness of drug

• Ec 50 - half of the effective concentration

pharmcodynamics

• most of the population achieving the therpeutic response

• a few achieving the toxic effect

• therpeutic utility curve

therapeutic range

• increase in concentration.- increase effect - synchronised

• delay in the PD - effect continues to rise as concentration falls

PK PD relationship

• as dose is given the concentration in the plasma slowly increases,  having a higher therpeutic response, then the response starts to decrease insteady of constantly increasing which is due to tolerance to the medication

• at the same concentration, the therapeutic effect is lower

hysteresis loop - counterclock wise

• drug concentration goes up, but the effect declines

• increase concentration - increase effect but then tolerance develops and effect declines before peak concentration

hysteresis loop - clockwise