Download - Farmakokinetik KLinik.2010ppt.ppt
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fath's 2010 1
Laboratorium Farmakologi FK-UMM
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fath's 2010 2
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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fath's 2010 3
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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fath's 2010 9
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fath's 2010 10
!"$+%$&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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fath's 2010 11
!onsentrasi /kadaro1at dalam plasmasetelah pem1erian per oral dan iv
per oral intra vena
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fath's 2010 12
*"'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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fath's 2010 13
Drug with low *d
A
D D
E
1arin&an 1arin&anla%ma
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fath's 2010 14
Drug with high *d
high tissuebinding
1arin&an 1arin&anla%ma
A
E
D D
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fath's 2010 15
0'%AA$0% ,-0l
0l ear2 &in1al2 la%ma2 or&an lain
t&t rate elimina%i
0l- Do%e (i,) - F9DoA!0 (i,) A!0o
Dosis tunggal
0l - rate eliminasi 0 plasma
= 8ol9 la%ma :& +iber%ikan +ari obat er %at'an @akt'
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fath's 2010 16
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Sum of all process
contributing to dis-appearance of drug
from plasma
Drug in plasma at
concentration of 2 g/ml
Drug concentration
in plasma is less after
each pass throughelimination/metabolism
process
Drug molecules disappearing from
plasma at rate of 400 g/min
CL = 400 g/min
2 g/ml
= 200 ml/min
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0l - R9 elimina%i
0 la%maR9 elimina%i - 09la%ma
0l
0 l ear B- aliran +r0 in metab 0 o't
R elimina%i - Bh90 in = Bh9 0 o't
- Bh( 0 in = 0 o't )
0l ear - Bh.( 0 in = 0 o't ) 0 in
- Bh9Eh(ratio ek%trak%i)
Example.Eh = 0.820%drug out from hepar enter to
portal e!n.
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0l ear ter&ant'n& a+a "
akti,ita% enCim
rotein la%ma
aliran +ara
ratio ek%trak%i
0l &in1al ter&ant'n& a+a "
;'n&%i &in1al
ikt obat +& rotein la%maaliran +ara ke &in1al
ratio ek%trak%i &in1al
'rine
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fath's 2010 20
3A'F '#F% - 4A!&2 (A23-t5/6
t./7 - >9 * 8+ T (inter,al +o%i%)
0l - t./7
o " =H * t./7 - 0%%
0%% - on%9%tea+: %tate
In;'% "0%% R el - R in;
0%% - R in;
0l
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Percentages of drug eliminated (1st-order elim.) after
different numbers of half-lives
#t1/2s % eliminated
1 50 = 50%
2 50 + 25 = 75%3 50 + 25 + 12.5 = 87.5%
4 50 + 25+ 12.5 + 6.25 = 93.75%
5 50 + 25 + 12.5 + 6.25 +3.125
= 96.9%
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fath's 2010 23
Accumulation Eample
Administer 5 g of drug at intervals ofits t5/6
1 g 0.5 g after one t1/2 gi!e 2nd dose" no# 1.5 g in
bod$.
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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fath's 2010 25
(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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fath's 2010 38
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