Kinetics Lecture 10-21 Part 19

Front 1

sustained-release dosage form

similar to the prolonged-release dosage form, in addition to slow, time-dependent drug release, it:

Back 1

releases a loading dose immediately

Front 2

pharmacokinetics in the sustained release form is similar to :

Back 2

the prolonged-release dosage form.
the loading dose needs to be considered

Front 3

in sustained-release dosage form

(first and zero order)

Back 3

the description will be derived for the prolonged-release phase with zero-order kinetics; the description for first order release can be obtained in the same way

Front 4

principle of superposition

early doses do not affect the pharmacokinetics of subsequent doses

Back 4

true

Front 5

principle of superposition

pharmacokinetics after multiple doses can be calculated using:

Back 5

data from a single dose

Front 6

principle of superposition

valid for :

Back 6

linear pharmacokinetics

Front 7

principle of superposition

exceptions:

Back 7

-severely non-linear pharmacokinetics
-enzyme induction
-enzyme inhibition
-changing pathophysiology

Front 8

cp: zero order release I

without loading dose:
(equation)

Back 8

cpp(t)= kro/ke * (1 - e^-ke * t)

Front 9

cp: zero order release I

loading dose Dl alone would result in:

Back 9

the hypothetical time course of plasma concentration given by the equation of one-compartment model:

cpl(t)= Dl/Vd * e^-ke *t

Front 10

cp: zero order release II

the plasma concentration is:

Back 10

the sum of the concentrations resulting from the extended release and from the loading dose

cp(t)= kro/ke + ( Dl/Vd - kro/ke) * e^-ke*t

Front 11

cp: zero order release

optimal loading dose, Dlo:

Back 11

will completely eliminate the time course of plasma concentration and ensure immediate onset of the steady state:

Dlo= kro * Vd/ke

Front 12

time course of plasma concentration

Back 12

see graph on page 2 slide 1

Front 13

delayed release dosage forms

the drug is released with:

Back 13

some delay (td) after the administration

Front 14

delayed release dosage forms

the release is:

Back 14

fast and treated as instantaneous

Front 15

delayed release dosage forms

pharmacokinetics is similar to pharmacokinetics of ordinary products, with the exception that the time term is modified
in place of t-->

Back 15

the term (t-td ) is used for the delayed dose

Front 16

enteric coated tablets:
fast absorption I

valid for:

Back 16

fast absorption- only the central compartment is used

Front 17

enteric coated tablets:

the time course of plasma concentration is similar to the conventional expression, in place of t, the term-->

Back 17

t-td is used

t < td: cp(t)= 0

t > or = td: cp(t)= D/Vd * e^-ke * (t-td)

Front 18

enteric coated tablets fast and slow absorption graphs

Back 18

see page 2 slide 4 and 6

Front 19

enteric coated tablets: slow absorption I

valid for:

Back 19

slow absorption and fast plasma/tissue equilibration- dosing compartment and central compartment are present

Front 20

enteric coated tablets: slow absorption I

the time course of plasma concentration is similar to the conventional expression, in place of t:

Back 20

t-td is used

t < td: cp(t) = 0
t > or = td: cp(t) = F* D/Vd * ka/ka-ke * [e^-ke * (t-td) - e^-ka * (t-td)]

Front 21

repeat action dosage forms

the first dose D1 is released:

Back 21

immediately after the administration


(instantaneous)

Front 22

repeat action dosage forms

the second dose D2 is released:

Back 22

with some delay (td), both processes are treated as instantaneous

Front 23

repeat action dosage forms

pharmacokinetics is given as :

Back 23

the sum of equations for individual doses (principle of superposition)

Front 24

repeat action dosage forms

the maximum plasma concentration can be higher than after one dose, if:

Back 24

the first dose is not completely eliminated at the time of the second dose

Front 25

repeat action dosage forms:
fast absorption I

valid for:

Back 25

fast absorption and fast plasma/tissue equilibriation- only central compartment is present

Front 26

repeat action dosage forms:

the time course of plasma concentration:

Back 26

t< td: cp(t)= D1/Vd * e^-ke * t

t> or = td: cp(t)= [cp(td) + D2/Vd] * e^-ke *(t-td)

Front 27

repeat action dosage forms:

there is no accumulation from the two doses if cp(td) = 0

Back 27

true

Front 28

repeat action dosage forms: fast absorption II

Back 28

see page 3 slide 3