11/26/2013

PHARMACOKINETICS
4th year
Multiple Extravascular

Extravascular Administration

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Estimating concentration in
Body after n Extravascular Doses
There is added level of complexity to determine
concentrations following multiple extravascular
doses because of F and ka.
ka
Following equations may be derived for
extravascular administration:
KaFXo ⎡ (1 − e − nKτ )e − Kt (1 − e − nKaτ )e − Kat ⎤
Cn = ⎢ − ⎥
Vd ( Ka − K ) ⎢⎣ 1 − e − Kτ 1 − e − Kaτ ⎥⎦

2.303 ⎡ Ka (1 − e − nKaτ ) 1 − e − Kτ ⎤
(tp )n = log ⎢ − nKτ
* ⎥
Ka − K ⎣ K (1 − e ) 1 − e − Kaτ ⎦

At Steady State
KaFXo ⎡ e − Kt e − Kat ⎤
Css = ⎢ − ⎥
Vd ( Ka − K ) ⎢⎣1 − e − Kτ 1 − e − Kaτ ⎥⎦

2.303 ⎡ Ka (1 − e − Kτ ) ⎤
(tp ) ss = log ⎢ − Kaτ ⎥
Ka − K ⎣ K (1 − e )⎦

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Accumulation Ratio
FXoe − Ktpss
( Css ) max Vd (1 − e − K τ )
R = =
( C 1 ) max FXo
e − Ktp
Vd

FXo ⎡ e − Kτ e − Ka τ ⎤
−
( Css ) min Vd ( Ka − K ) ⎢⎣ (1 − e − K τ ) (1 − e − Ka τ ) ⎥⎦
R = =
( C 1) min FXo
K −K)
Vd ( Ka
[
e − K τ − e − Ka τ]

( Css ) min 1
R = = − Kτ
( C 1 ) min (1 − e )( 1 − e − Ka τ )

If the dosing interval is long so that the next

dose is given in the post-absorption phase then
all the three equations become equal to each
other
1
R =
(1 − e − K τ )
Time to Reach Steady state

e − nKa τ
K Ka e − nK τ
fss = 1 + −
Ka − K Ka − K
If Ka/K≥ 10

nτ = − 1 . 44 t 0 . 5 ln( 1 − fss )

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FXo 1.44t0.5 FXo

FX FX
C av = KVdτ = Vd * τ
ss

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A 500-mg dose of the sulfonamide

sulfamethoxazole is administered as an oral
tablet to a human subject. Eighty percent of
the drug is absorbed, and the balance is
excreted unchanged in feces. The drug
distributes into an apparently homogeneous
body volume of 12 L, and has an absorption
half-life of 15 min and overall elimination
half life of 12 h.
half-life h Calculate the following :
(i) tmax and
(ii) C max. after the first dose and at steady
state if the drug is administered twice daily.

An oral multiple dosing regimen of tetracycline

250 mg capsules was instituted for adult subject
weighing 81 kg. the dosing frequency was set at
four times per day.
provided following kinetic data for the drug
• Bioavailability = 75%
• Elimination half-life = 10 hours
• Absorption rate constant = 0.45 h-1
• Apparent vol. of dist. = 1.5 L.kg-1
Estimate the following
- tmax,
tmax Cmax
Cmax, and Cmin after the first dose (4.91
(4 91 hr,
hr
1.1 mg/L, ),
- tmax, Cmax, and Cmin at steady state
- the plasma concentration 4 hours after 7th dose
- the accumulation ratio of the drug