Farmakokinetik KLinik.2010ppt.ppt

7/25/2019 Farmakokinetik KLinik.2010ppt.ppt

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fath's 2010 1

Laboratorium Farmakologi FK-UMM


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Tujuan Belajar

Diharapkan mahasiswa mampu :Menjelaskan aplikasi farmakokinetik

pada therapeutic drug monitoringMenghitung regimen dosis secaraindividual dengan menggunakandata farmakokinetik untukmendapatkan efek terapi maksimumdan efek toksik yang minimum.

Menjelaskan penyesuaian regimendosis pada kondisi pasien tertentu


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FAMA!"!#$%! !'#$#!

Prinsip-2 farmakokinetik (dasar)klinik FARMAKOTERAPI

REGIMEN DOSIS

Data FK obat Parameter

??


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DOSIS (R/)

DOSIS G DIMIN!M

Faktor FK " A D M E

KONSENTRASI O#ATDI TEMPAT KER$A

Fi%iolo&ik

Patolo&ikGenetik

!m'r

Interak%iFaktor FD "

re%etor omeo%tatik

EFEK / RESPON P*


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(arameterFarmakokinetik

BioavailabilitasKonsentrasi / kadar obat

olume distribusi

!learan"e#alf-life / $aktu %aruh

&hera%euti" $indo$

egimen dosisKoreksi dosis (%en)akit*


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)#"A*A#'A)#'#&A+ ,-F

=Fraksi dosis obat di sirkulasi dalam bentuk aktif

eliminasi

ab%or%i

+i%trib'%i

i, F - .

o F .

F oral (ab%ol't) - A!0 o A!0 i,

iv

po


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!"$+%$&A+#/ !ADA ")A&,-0

+i temat ker1a re%etor2 1arin&an

*O#AT SIRK!3ASI TEMPAT KER$A4 5 4 5

mo+el . komartemen

6O#AT SIRK!3ASI SENTRA3 (la%ma21ant'n&2

ear2&in1al)

PERIFER (otot2 k'lit)

mo+el 7 komartemen


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!onsentrasi /kadaro1at dalam plasmasetelah pem1erian per oral dan iv

per oral intra vena


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*"'2M% D#+)2+# ,-*d

8ol9 Pen:ebaran obat

+lm t'b'

(ima1inati;)

1ml9obat +i tb

kon%9l%ma (0)

8+ - < - Di, - F9Do0 0i,=> 0o

-+ien&ar'i ole "'k'ran ? komo%i%i t'b'2 ;'n&%i k,%2kemam'an mol9obat mema%'ki 1arin&an2

ikt9 rot la%ma


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Drug with low *d

A

D D

E

1arin&an 1arin&anla%ma


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Drug with high *d

high tissuebinding

1arin&an 1arin&anla%ma

A

E

D D


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0'%AA$0% ,-0l

0l ear2 &in1al2 la%ma2 or&an lain

t&t rate elimina%i

0l- Do%e (i,) - F9DoA!0 (i,) A!0o

Dosis tunggal

0l - rate eliminasi 0 plasma

= 8ol9 la%ma :& +iber%ikan +ari obat er %at'an @akt'


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Sum of all process

contributing to dis-appearance of drug

from plasma

Drug in plasma at

concentration of 2 g/ml

Drug concentration

in plasma is less after

each pass throughelimination/metabolism

process

Drug molecules disappearing from

plasma at rate of 400 g/min

CL = 400 g/min

2 g/ml

= 200 ml/min


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0l - R9 elimina%i

0 la%maR9 elimina%i - 09la%ma

0l

0 l ear B- aliran +r0 in metab 0 o't

R elimina%i - Bh90 in = Bh9 0 o't

- Bh( 0 in = 0 o't )

0l ear - Bh.( 0 in = 0 o't ) 0 in

- Bh9Eh(ratio ek%trak%i)

Example.Eh = 0.820%drug out from hepar enter to

portal e!n.


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0l ear ter&ant'n& a+a "

akti,ita% enCim

rotein la%ma

aliran +ara

ratio ek%trak%i

0l &in1al ter&ant'n& a+a "

;'n&%i &in1al

ikt obat +& rotein la%maaliran +ara ke &in1al

ratio ek%trak%i &in1al

'rine


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3A'F '#F% - 4A!&2 (A23-t5/6

t./7 - >9 * 8+ T (inter,al +o%i%)

0l - t./7

o " =H * t./7 - 0%%

0%% - on%9%tea+: %tate

In;'% "0%% R el - R in;

0%% - R in;

0l


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Percentages of drug eliminated (1st-order elim.) after

different numbers of half-lives

#t1/2s % eliminated

1 50 = 50%

2 50 + 25 = 75%3 50 + 25 + 12.5 = 87.5%

4 50 + 25+ 12.5 + 6.25 = 93.75%

5 50 + 25 + 12.5 + 6.25 +3.125

= 96.9%


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Accumulation Eample

Administer 5 g of drug at intervals ofits t5/6

1 g 0.5 g after one t1/2 gi!e 2nd dose" no# 1.5 g in

bod$.

1.5 g 0.%5 g gi!e &rd dose" no# 1.%5 g in bod$.

1.%5 g 0.'' g gi!e t dose" no# 1.'' g in bod$.

1.'' g 0.* g gi!e 5t dose" no# 1.* g in bod$.

1.* g 0.*% g gi!e +t dose" no# 1.*% g in bod$.

1.*% g 0.** g gi!e %t dose" no# 1.** g in bod$.


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Faktor yang Mempengaruhit

,sia Fungsi enal (ekskresi)

Fungsi epar (metabolisme)

katan Plasma Protein


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(lasma t5/6of Drugs in 7oung Adult

and %lderly (atients

Drug 20-30 r 65-80 r

"en!#!ll!n 21 m!n 39 m!n

$etra##l!ne 3.5 hr 4.5 hr &!go!n 51 hr 73 hr

"heno(ar(!tal 71 hr 107 hr

&!a)epam 20 hr 80 hr


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!hole-"od# t$/2%hour& 'alues !ith and !ithout

(enal )ailure

Drug $ormal enalfailure

+ 0ephale8in 5.9 59.9

+ 'incomycin 9. ;. .5


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%@#M%$ D"+#+

PEREN0ANAAN PEM#ERIAN O#AT !/PERIODE JAKT! TERTENT!

MENGASI3KAN KONS9O#AT G

DIINGINKAN ( 0 terai / 0 tar&et )

= t+k melebii kon%9tok%ik min

= t+k kon%9teraetik min

TERAPE!TI0 JINDOJS


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Terae'ti @in+o@%


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TERAPE!TI0 JINDOJS

+i&'nakan '/ menent'kan bata% kon%9la%ma:& +aat +iterima

'/ re&imen +o%i%

DOSIS MAINTENAN0E (en'n1an&) - Dm

$k erl' %e&era menaai kon%9T* / tar&et

DOSIS AJA3 (3OADING) - Dl


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'A$@!A3 M%$%$&2!A$%@#M%$ D"+#+

.9 Tent'kan kon%9t* / 0 tar&et / nilai ten&a ran&e terai

In;'% 09tar&et - 0%% - R9in; R9in; - 0%% * 0l

0l Dm - 09tar&et * 0l

Oral 09tar&et - 0%%9a, - F9Dm * .

T 0lDm - 09tar&et * 0l

t./7 F


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79 Do%i% a@al/ Dl

#ol'% I8 Dl - 0tar&et * 8+

Oral Dl - 0tar&et * 8+F

Pen&it'n&an re&imen +o%i%

Data 0l2 F2 8+2 t ./7

0%%

0ek / 'k'r +i la%ma


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3. Sampel darah

diambil 4 - 5 x t 1/2, sebelum dosis berikut4. Penyesuaian regimen dosis !SP"# $%&$'''

$adar plasma

penyesuaian dosis

(osis baru = (osis lama ) target p yg diukur


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In+i,i+'ali%a%i

6 Obat +& T* @in+o@% %emit ( +i&o*in2 ;enitoin2teo;ilin2 +ll)

6 Ka+ar la%ma ber,aria%i ( roanol2 teo;ilin2

;enitoin2 %ali%ilat2 +ll )

6 P* atolo&ik k,%2 &in1al2 ear

6 Ga&al terai


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&herapeutic Drug Monitoring

erapeuti range" aro*imationof a,era&eplasma drug onentrations tat are safe andeffiaious in 34 patients.

sould not be onsidered absolute

eop$lline"6 4ome patients" 784 to9iiti$ at :20 mg/m;

6 4ome patients"


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0ommonly Monitored Drugs=mikain 20-&0 mg/ m;

7arama>epine -12 mg/m;Digo9in 1-2 ng/m;

?entamiin 5- 10 mg/m;

;idoaine 1-5 mg/m;

;itium 0.+-1.2 m


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&DM Functions/ (arameters

+ ,ele"t rug+ esign dosage regimen

+ .valuate %atient res%onse

+ etermine need for measuring drug levels

+ ssa) for drug+ erform K evaluation of drug levels

+ e-adust dosage regimen

+ Monitor serum drug levels+ e"ommend s%e"ial reuirements


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Kasus

+ ,eorang gadis 13 tahun (BB4 50kg* diba$a ke rumah

sakit dengan sesak nafas )ang berat6 iagnosa dokteradalah status asmatikus dan harus ra$at ina%6 enderitaakan diberi teo7liin i6v6 sebagai 8loading dose9 untuksegera mengatasi sesakn)a6 iketahui datafarmakokinetik teo7lin d40:5L/kgBB: !learan"e 4 ;L/am:dan konsentrasi )g dihara%kan (target* 4 10 mg/L6

1. Bera%a 8loading dose9 teo7lin )ang diberikan se"arai6v6 0:? = ?

4 ;0mg/am > 0:? = ? am4 ;00mg /? am

mino7lin 4 ;00 > ?0@/? am4 ;A5mg amino7lin/?am

Farmakokinetik KLinik.2010ppt.ppt

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