Flashcards in 1: Clinical Pharmacokinetics 2 Deck (27)
what are the three components of renal clearance?
CLrenal = filtration + secretion - reabsorption
what is a normal GFR?
what types of drugs are filtered by the glomerulus?
only unbound drugs
what are two markers for GFR?
creatinine and inulin
-unbound to plasma proteins
-neither secreted nor absorbed
-about 100 mL/min
renal clearance and dosage adjustment + corrected dose equation
renal disease often changes drug clearance -> this can be used to adjust dose to maintain the Css
corrected dose= avg dose (pt CLcreatinine/ 100 ml/min)
when do you adjust dosages?
only when drug is >50% cleared by renal elimination and renal fxn is reduced to 50% or less of normal
first order elimination
-constant % of drug eliminated/time
-when drug dose increases, Css increases proportionately
-how 95% of drugs work
-accumulation + elimination change exponentially for a single dose over time
-linear Cp accumulation with increase in dose
zero order elimination
-constant amount of drug eliminated/time
-ER same regardless of [C]
-linear decrease in [C] over time
-non-linear Cp accumulation with increase in dose
Michaelis-Menton kinetics: rate of elimination
= (Vmax x C)/(Km + C)
definition of Km
[drug] at 50% of Vmax
-measure of the affinity of the substrate for the enzyme
definition of half life
time it takes to eliminate 50% of the drug from the body - only applies to first order drugs
what is the elimination rate constant?
K or Ke - fraction of Vd elimination remains constant per unit time
equation for half life
= 0.693/ Ke = (0.693 x Vd)/ CL
is half life dependent on concentration?
describe the accumulation and elimination of a drug according to half-lives
95% of final accumulation plateau reached after 4.5x
95% of total dose eliminated after 4.5x
why is half life important? (3 reasons)
1. determine time to reach Css
2. determine duration of action
3. determine proper dosing frequency to avoid large fluctuations in Cp
how will doubling the dose administered change the duration of action?
increases duration by one half life
one compartment model: Vd with elimination
-equation for Vd
Vd = dose/Co
-body is ONE homogeneous compartment
two compartments: Vd distribution without elimination
-distribution b/w compartments slower than distribution within each compartment
-distribution phase typically
two compartments: Vd distribution with elimination
-distribution to 2nd compartment slower than distribution w/i 1st compartment
two compartment model assumptions
-instant mix in 'each' compartment
-slower mix 'between' compartments
designing dose regimens for i.v. vs p.o: DR
iv: DR = (CL)(Css)
po: DR = (CL x Css)/F
designing dose regimens for i.v. vs p.o: loading dose
iv: loading dose = (Vd)(target Cp)
po: loading dose = (Vd x target Cp)/F
designing dose regimens: therapeutic window at different values of half life
-if dosing interval = t1/2, Cmax/Ctrough = 2
-if dosing interval t1/2, Cmax/Ctrough > 2 (may exceed therapeutic window)
equation to adjust dosage regimen
new rate = (old rate)(desired Css/ measured Css)
what is the purpose of therapeutic drug monitoring?
use Cp to: