Ex 2. L1: Multiple Dosing Regimen Flashcards
Infusion vs multiple dosing
Infusion - starts from low conc, slowly goes up until it reaches steady state where the rate of drug going in and rate of drug coming out are equal
ex. 100m/hour infusion = 2,400 mg/day
Multiple: 200mg * 12/day = 2,400mg
Multiple doses
(Jagged curve)
Do you reach steady state at the same time and capacity with infusion vs multiple dosing
Yes (3.3 half lives to reach steady state)
Principles of drug accumulation: IV bolus
First dose: concentration is pretty high, gets lower after time because of elimination
Dose 2 profile will be exactly the same as start of dose 1 profile
Total concentration =
Concentrations at the same hour added up
(i.e hour 73: Dose 1 (0.47) + dose 2 (1.30) + dose 3 (3.5) + dose 4 (9.6) = 14.87 mg/L
Multiple dose:
Peak: Cmax
Trough: Cmin
Put the dose number in front of the Max (i.e. looking at dose 4, we say C4Max)
Tau (T): Dosing interval
Dose exposure:
Exactly the same under different doses
(trapezoid rule AUC)
Accumulation index (Rac)
C0 [1/1-e^-kt]
Accumulation index Rac example
20mg q24h
10mg q12h
More accumulation for 10mg q12h
Less frequent dosing (i.e. larger T) leads to…
Smaller accumulation index
Larger dosing interval (T) leads to
Greater fluctuation
Longer dosing intervals and fluctuation
When you give a drug q24, drug will have longer time to be eliminated, concentration drops more before next dose, more fluctuation with longer dosing intervals
Infusion has greater (accumulation/fluctation)
Fluctuation
Multiple dose has more (accumulation/fluctation)
Accumulation
Average concentration at steady state: same amount of dose admin per unit time will lead to
Same CSSave
Average concentration:
Concentration that gives same AUCss,0-T when maintained for T
