BAHAN AJAR UNTUK TOPIK MINGGU KE-7

TOPIC 7 : KINETIKA MICHAELIS-MENTEN

MATA KULIAH :

FARMAKOKINETIKA

Disusun oleh PJMK :

M.M. Farida Lanawati Darsono, S.Si.,M.Sc

Semester Genap
Tahun Akademik : 2021-2022

Universitas Katolik Widya Mandala Surabaya

Fakultas Farmasi

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 TOPIC 7 : KINETIKA MICHAELIS-MENTEN

Pustaka tambahan :
https://slideplayer.com/slide/7688300 = Quantitative
Pharmacokinetics - Non Linier Pharmacokinetics by Dr Charlet Tan

Capacity-Limited Metabolism (CLH ,F)

 Enzymatic reactions are saturable.

Vmax [ S ]
v
K m  [S ]

 Saturated hepatic metabolism decreases CLH.

 Saturated first-pass metabolism increases F.

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e. g. - capacity-limited metabolism
- Phenytoin is eliminated by
hepatic metabolism only.
- As the dosing rate
increases, Cp increases
disproportionally.
- As the dosing rate
increases, hepatic
metabolism is saturated and
CL decreases.
- As the dosing rate
increases, it takes longer
time to reach steady state.

FD
 CL Css
 24

e. g. - capacity-limited metabolism
- Phenytoin is eliminated by
hepatic metabolism only.
- As the dosing rate
increases, Cp increases
disproportionally.
- As the dosing rate
increases, hepatic
metabolism is saturated and
CL decreases.
- As the dosing rate
increases, it takes longer
time to reach steady state.

FD
 CL Css
 24

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 Maintenance Dose Selection for Phenytoin

- Phenytoin is eliminated
by hepatic metabolism
(CYP2C9) only.
-Variability in Vmax and Km
values in patients causes
a wide range in the
effective doses needed to
achieve therapeutic
levels.

therapeutic range= 10-20 g/ml

= 10-20 mg/L
34

Maintenance Dose Selection for Phenytoin

A patient has been taking phenytoin (PHE) 150 mg b.i.d for 4

months. His plasma levels of PHE averaged 5 mg/L on this
dose. Adjustment in dose to 250 mg b.i.d eventually led to a
new plateau level of 20 mg/L. Assuming true steady state,
strict patient compliance and that the measured plasma
concentrations represent average levels over the dosing
interval.

a) use a graphical method to estimate the patient's operative

Vmax/F and Km values;

b) estimate a daily dose which should provide a steady-state

plasma level of 12 mg/L.
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