PERAN PARAMETER FARMAKOKINETIK DALAM TERAPI

Mata Kuliah : FarmakokinetikDosen Pengampu : Rovina Ruslami, dr.,

SpPD, PhD

Oleh : Neni Anggraeni (130120150011)

Parameter farmakokinetika adalah besaran yang diturunkan secara matematis dari model yang berdasarkan hasil pengukuran kadar obat utuh atau metabolitnya dalam darah, urin atau cairan hayati lainya. Parameter farmakokinetik suatu obat ini dapat digunakan untuk memperoleh gambaran dan mempelajari suatu kinetika absorpsi, distribusi dan eliminasi didalam tubuh.

Volume Of Distribution

Volume of distribution (V) relates the amount of drug in the body to the concentration of drug (C) in blood or plasma:

Volume distribusi dapat berubah karena umur, jenis kelamin, dan penyakit

Obat yg terikat dgn protein plasma, sebagian besar obat berada didalam darah maka volume distribusinya akan mempunyai batas terendah. (warfarin & klorpropamid)

Clearance

Drug clearance principles are similar to the clearance concepts of renal physiology. Clearance of a drug is the factor that predicts the rate of elimination in relation to the drug concentration (C)

Clearance, like volume of distribution, may be defined with respect to blood (CLb), plasma (CLp), or unbound in water (CLu), depending on where and how the concentration is measured.

Clearance

Elimination of drug from the body may involve processes occurring in thekidney, the lung, the liver, and other organs.

Clearance

Capacity-Limited Elimination

Most drug elimination pathways will become saturated if the dose and therefore the concentration are high enough. When blood flow to an organ does not limit elimination, the relation between elimination rate and concentration (C) :

Half Life

Half-life (t1 /2) is the time required to change the amount of drug in the body by one-half during elimination (or during a constant infusion).

The time course of drug in the body will depend on both the volume of distribution and the clearance:

Bioaviability

A RATIONAL DOSAGE REGIMEN

A rational dosage regimen is based on the assumption that there is a target concentration that will produce the desired therapeutic effect. Penentuan Dosis berdasarkan :•Jumlah obat yang diberikan dalam satu waktu•Cara pemberian•Jarak waktu diantara dua dosis•Lama waktu pemberian obat

Maintenance DoseAt steady state, the dosing rate (“rate in”) must equal the rate of elimination (“rate out”). Substitution of the target concentration (TC) for concentration (C) in equation predicts the maintenance dosing rate:

Maintance Dose = Dosing rate x Dosing interval

Loading DoseThe volume of distribution is the proportionality factor that relates the total amount of drug in the body to the concentration; if a loading dose is to achieve the target concentration

Efek Penyakit Terhadap Proses Farmakokinetik

Keadaan patologis dapat merubah semua parameter farmakokinetik

Umumnya kelainan hati dapat mengurangi clearance dan memprlama half time obat. Tetapi pada obat-obat tertentu terjadi sebaliknya.Contoh : tolbutamid pada penyakit hepaitis virus akut.

Perubahan farmakokinetik pada penyakit ginjal dapat diterangkan dengan konsep clearance. Cl ginjal = (Cl RF + Cl RS) x (1-FR)

Ekskresi ginjal di tentukan oleh Filtrasi, sekresi aktif, dan reabsorpsi.Filtrasi : Volume cairan yg difiltrasi & konsentrasi obat yg tidak terikat didalam plasma.