Clinical Pharmacokinetics Flashcards
renal clearance
CLrenal = filtration + secretion - absorption
For reabsorbed drugs, renal CL is dependent on
urine flow rate
markers for GFR
creatinine and insulin
Normal glomerulus filtration rate (GFR)
120 mL/min
properties of creatinine and insulin
unbound to plasma proteins
neither secreted nor reabsorbed
about 100mL/min
Adjusted/Corrected dose to maintain Css (in renal disease) =
average dose * (Patients’ creatinine clearance/100 mL/min)
When is dose adjustment necessary?
when a drug is >50% clearned by renal elimination and renal function is reduced to half of normal or less
What do you do if other elimination routes are involved (liver)?
the corrected dose should be the sum of adjusted dose for each elimination route
Corrected dose = adjusted dose for renal + adjusted dose for liver
First order elimination
when the drug dose is increased, the Css will increase proportionately
DR =
CL * Css
At steady state, DR =
ER = CL * Css
95% of drugs within their therapeutic range of concentration fall under which type of elimination
first order elimination (accumulation and elimination of the drug change exponentially)
5% of drugs at their therapeutic concentration fall under which type of elimination
zero-order elimination (the drug elimination capacity is saturated)
ER =
CL * Cp
drug elimination rate as a result of zero-order elimination
drug elimination rate is constant regardless of drug concentration (decrease will be in a linear fashion, accumulation of drug concentration will be non-linear)
drug examples of zero-order elimination
ethanol (over most of its Cp range)
phenytoin and aspirin (high therapeutic or toxic concentration)
First order elimination
the amount of drug eliminated per unit time is proportional to [C]; same % of drug is eliminated per unit time
Zero order elimination
a constant amount of drug is eliminated per unit time; same AMOUNT of drug is eliminated per unit time
What happens when you increase a dose with a first-order elimination drug?
Cp is linearly accumulated along with the DOSE
What happens when you increase a dose with a zero-order elimination drug?
Cp is non-linearly accumulated along with the DOSE (elimination is limited because it is saturated)
Rate of elimination =
Vmax * C / Km + C
Michaelis-Menten Kinetics
Vmax
the max velocity of a reaction at very high drug concentration
Km
the drug concentration at 50% of Vmax; a measure of the affinity of the substrate to the enzyme
What assumptions do you need to ask about drugs before you can do calculations?
If this drug first-order or zero-order elimination?
