1: Clinical Pharmacokinetics Flashcards
equation for concentration
[C] = M/V
pharmacokinetics (PK) vs. pharmacodynamics (PD)
PK: what the body does to the drug
- how the [drug] changes as it moves through different compartments of your body
- drug disposition: ADME
PD: what the drug does to the body
- describe the relationship b/w the [unbound drug] at the receptor and drug response
- potency, drug effect
PK predicts PD
fundamental hypothesis simple statement
predictable relationship b/w plasma (or serum) concentration of drug and its effect
3 general goals of PK
- establishing/adjusting dosage regimens
- diagnosis of toxicoses
- withdrawal times for food safety in babies
AUC
area under the curve - describes the ‘behavior’ (exposure) of the drug moving through the body
bioavailability, F
% of drug entering into circulation
= (% absorbed)(1-Eh)
=AUC (p.o.)/ AUC (i.v.)
Eh (hepatic extraction ratio)
fraction of drug extracted by liver in FPM
=(C1-C2)/C1
effects of hepatic extraction on bioavailability
low Eh drugs have higher F
-changing enzymatic activity doesn’t significantly change Cp
high Eh drugs have lower F
-changing enzymatic activity does significantly change Cp
relative bioequivalence, Fr
= AUC generic/ AUC brand
two considered equivalent if 0.8
which form of a drug is active: bound or unbound?
unbound
apparent volume of distribution, Vd
-constant relating the amount of drug in the body to the plasma drug concentration
= total drug in body (A)/ plasma [drug] (Cp)
why can Vd be much larger or smaller than the physical volume?
uneven distribution in different compartments
factors affecting Vd
- MW (drug)
- polarity (drug)
- permeability (drug)
- solubility (drug)
- BINDING (drug and patient)
- blood vol/flow (patient)
- size of organ (patient)
- transporters (patient)
- disease status (patient)
steady state concentration, Css
[drug] where rate of drug input = rate of drug elimination
maintenance dose rate, DR
rate of drug input to maintain the [drug] at steady state
= (CL)(Css)
loading dose vs. maintenance dose
loading dose reached Css faster than maintenance dose
loading dose
= (Vd)(target Cp)
definition of drug metabolism
IRREVERSIBLE transformation of parent compounds into daughter compounds –> can either terminate action or bioactivate
what is the path by which most drugs are excreted?
renal
clearance, CL
volume of drug eliminated per unit time
-constant for drug and patient
= dose/ AUC
=
elimination rate, ER
mass of drug eliminated per unit time
= (CL)(Cp)
elimination rate constant, K or Ke
percent of drug eliminated per unit time
= CL/Vd
when DR remains the same, how will changing CL alter Css?
changing CL will proportionately and inversely change the Css
organ x clearance, CLx
= organ extraction ratio (Ex) x organ blood flow (Qx)
for drugs extensively metabolized by the liver, describe how Eh and Q affect CL
Eh is almost fixed and will barely affect CL, so CL will mainly be determined by Q
-important for drug-drug interactions when hepatic drug metabolism is induced/inhibited and in certain conditions that affect blood flow
for drugs with high Eh, how will increased hepatic metabolism affect F and CL?
decreased F
no change in CL
for drugs with low Eh, how will increased hepatic metabolism affect F and CL?
no change in F
increased CL
