Chronic Dosing: Bolus Dosing Flashcards
(9 cards)
What are the components of multiple bolus dosing
dose + dosing interval (tau)
—conc fluctuate within dosing interval bw peak and trough
SS idea still exists but not Css itself (fluctuates)
- degree of fluctuations based on timing bw doses
What happens when dosing interval is equal to t1/2
amount of drug in body at the end of the interval —- equal to 50% of max drug in the body (aka eliminates half)
- as number of doses increases == more eliminated
C after dose = dose + C left from last dose (max C)
SS: when amount in (dose) = amount eliminated by end of dosing interval
—— amount of drug in body increases till you reach this point
Css
- calculate max and min concentrations after number of doses
min C: dependent on max C, k, and dosing interval
can also determine Css avg
What reflects the extent of accumulation
reflects the difference bw C at ss and those after 1st dose
ratio: Cssmax/Co
accumulation index: 1/1-e ^-k (tau)
What impacts the extent of accumulation
Depends on dosing interval + t1/2 or k
- if half life is constant: more frequent dosing results in more accumulation
- if short t1/2 + dosing not often: very very little acccumulation
- long t1/2 + give dose often: almost no elimination bw doses + accumulation will be high
What is the best way to calculate Cl
using AUCss and Dose
Why is k hard to calculate
hard to calculate bs dosing interval is not usually long enough for accurate estimation
- to get accurate k: need samples for 3-4X t1/2
common approach estimate k by collecting extra samples after final dose admin (can’t do in real pts)
What needs to be considered if multiple oral boluses
F and rate of A
C max: not only impacted by dose, V but also F and roA
What assumptions are made for multiple extravascular dosing
- most drugs have faster A than eliminaiton
—- can ignore rate of A and focus only on F
** not accurate for MR drugs are non oral routes of admin where A is slow
