Kinetics Lecture 11-02 Part 24

Front 1

slow plasma/tissue distribution

compartment model

Back 1

dosage form- central - tissue compartment

Front 2

slow plasma/tissue distribution

elimination

Back 2

from the central compartment

from the tissue compartment also possible

Front 3

volume of distribution

drugs with slow plasma/tissue distribution have:

Back 3

time-dependent volume of distribution

Vdi= initial Vd
Vdb = terminal Vd (elimination phase)

Front 4

steady state Vd

Vss=

Back 4

drug amt in body at ss/plasma conc at ss

Vdi < Vss < Vdb

Front 5

loading dose (fast distribution)

aim:

Back 5

fast achievment of the steady-state (plateau) concentration css

Front 6

immediate onset of css

the time-dependent term vanishes if:

Back 6

the loading dose had the optimal size, Dlo

Dlo= R/ke

Front 7

bolus + infusion

another way of description- as the drug amount

Back 7

- if the loading dose leading immediately to ss level is Dlo= R/ke

can be rewritten for the drug amount in plasma
Dp=Dlo + (Dl-Dlo) * e^-ke * t

Front 8

bolus + IV infusion for slow plasma/tissue distribution

similarity to:

Back 8

fast distribution (ss level Dss=Vss*css= R/ke)

Front 9

bolus + IV infusion for slow plasma/tissue distribution

difference:

Back 9

slow equilibrium into the tissue compartment, therefore the optimal loading dose 'CANNOT' be calculated by analogy with the fast plasma/tissue concentration as Dlo=R/ke

Front 10

bolus + IV infusion for slow plasma/tissue distribution

the loading dose may result in plasma levels that remain too high until distribution is finished

Back 10

true

Front 11

bolus + IV infusion for slow plasma/tissue distribution

solution:

Back 11

several lower loading doses further apart