PK Single IV dose Flashcards
(26 cards)
Why doesn’t concentrations of drugs not continuously rise forever when dose chronically?
1st order elimination
How to tell if one compartment model vs 2
1 compartment model: if plot LogC vs T + get straight line === 1 compartment model
2 compartment model: two different slopes/areas
T or F: in one compartment model, its monophasic and slope= k
T
- they undergo 1st order elimination
k = 1/time units
- body is a single space which drug has an input and output (determined rate by k)
What are the assumptions for one compartment model
drug distributes throughout body right away following admin + elimination starts right away
- highest C @ T=0 then declines
conc are identical everywhere in body but rates of elimination are
What is the elimination rate constant
k
- ranges from 0-1; fraction of the amount of drug in body eliminated per unit time
Calculate
- lnC vs T: slope =-k
- log C vs T: slope = -k/2.3
- semi log: Slope = -k/2.3
What is elimination half life (t1/2)
related to k (increase in K, decrease in t)
- helps determine dosing interval and length of time to get to SS when dose chronically
—— if higher t1/2 : takes longer to get to SS ‘
** k + t1/2 represent persistence in the body
Volume of distribution
V= dose/Co or V= Cl (total) /k
- volume at which drug appears to be distributed (tells if stays in plasma)
lower limit - plasma v
no upper limit
Clearance
v of blood/plasma from which drug is irreversibly removed (include all the ways drugs leave)
- Cl = k* V
——- Cl and V : independent
——- K: dependent
UL : BF to kidney and liver??
What is AUC
reflects the total exposure of body to the drug; related to Cl
— AUC 0- infinity = Dose/Cl total
—— AUC : dependent, Cl = independent
- if change Cl: AUC will change (change to AUC doesn’t change CL)
How to get AUC 0-infinity
Take AUC form o-t + Clast/k
- easy to get AUC this way
negatives: errors may occur; ideal when AUC total to be < 10% of AUC total
—— estimate highly dependent on k
What is AUMC
area under the curve x time x time curve
- area under the movement curve
What is mean residence time
any length of time a drug molecule spends in the body
- related to t1/2 but always > than it
- depends on k and reflects persistence
MRT = 1/k
** useful when RoA different and want to compare
MAT : MRT po - MRT iv etc
2 compartment model
when plot log C vs Time = not straight line
—- biphasic with initial rapid decrease in conc because redistribution from central comparement to peripheral
— central : blood and highly perfused tissues + organs that eliminate drug
— peripheral: SoA and poorly perfused tissues
** eventually get to equilibrium when conc lower
—- start to look linear like 1 compartment === now slope can be used to get k
As Cl decreases… K will and T1/2 will
k = decrease
T1/2- increase
T1/2 is also dependent on V ( even if Cl is high, if V high == only small amount of drug that can be cleared
CL UL - BF
V UL = nothing
What happens to V if Cl doubles
nothing — independent of each other
Formula for 2 compartment model
C(t) = A e ^ - alpha T + B e^ -beta T
A = distribution phase
Beta= elimination phase
RLS: elimination of drug
In 2 compartment model, what is happening to Elimination and distribution where T 0
nothing
- as T increases — central compartment conc increases but also decreases as some goes to 2nd or is eliminated
- T increases further : equilibrium bw 2 compartments == elimination phase now
What is B
intercept from the elimination phase
beta = slope for 2nd compartment
— use slope formula to get beta (basically k) ; don’t include distribution phase points
How would you get A and alpha
method of residue all
- plot differences bw concentration and extrapolated conc (actual - extrapolated)
- plot these vs time to get line
slope = -alpha and A is intercept
T or F: alpha > beta
T
What is T1/2 = to
t12 = 0.693/beta
What is the Vc equal to
Vc = dose/Co
What is Vss /Vt
V ss = sum of Vc and Vperipheral
-hard to get so use Vb instead
Vb =( dose/AUC) * beta
Difference bw 1st order elimination and zero order
1st : depends on concentration of drug (elimination higher when conc is higher); non linear when plot C vs T
- to make linear plot log or ln Conc
zero: constant (elimination doesnt’ change) ; linear relation when plot Conc vs T
