Individualization of drug dosage regimen.ppt

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K.P. ARUNK.P. ARUNLECTURERLECTURER

DEPARTMENT OF PHARMACY PRACTICEDEPARTMENT OF PHARMACY PRACTICE

JSS COLLEGE OF PHARMACY JSS COLLEGE OF PHARMACY

OOTY OOTY


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INTRODUCTIONINTRODUCTION

ALL HUMANS ARE ALIKE - True only a a S!e"#eALL HUMANS ARE ALIKE - True only a a S!e"#e

D#$eren"e e%#& - #n"lu'#n( &)e#r re!on#*eneD#$eren"e e%#& - #n"lu'#n( &)e#r re!on#*ene&o 'ru(&o 'ru(

T)ere+ore, &)ere # a +reuen& nee' &o &a#lor 'ru(T)ere+ore, &)ere # a +reuen& nee' &o &a#lor 'ru(a'#n#&raon &o &)e #n'#*#'ual !aen&a'#n#&raon &o &)e #n'#*#'ual !aen&

A +a#lure &o 'o o lea' &o #ne$e"*e &)era!y #nA +a#lure &o 'o o lea' &o #ne$e"*e &)era!y #n

oe !aen& an' &o%#"#&y #n o&)eroe !aen& an' &o%#"#&y #n o&)er

T)ere+ore, &)e a#n ")allen(e #n 'e#(n#n( aT)ere+ore, &)e a#n ")allen(e #n 'e#(n#n( a/&an'ar'0 'ru( 'oa(e re(#en # &)e *ar#a1#l#&y/&an'ar'0 'ru( 'oa(e re(#en # &)e *ar#a1#l#&y#n 'ru( )an'l#n( &)a& e%#& +ro !aen& &o !aen#n 'ru( )an'l#n( &)a& e%#& +ro !aen& &o !aen&&


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INTRODUCTION2INTRODUCTION2Un'er&an'#n( &)e our"e o+ &)# *ar#a1#l#&y an'Un'er&an'#n( &)e our"e o+ &)# *ar#a1#l#&y an'a'3un( 'ru( 'oe a""or'#n(ly # an area #na'3un( 'ru( 'oe a""or'#n(ly # an area #n

4)#") !)ara"#& "an a5e a a3or #!a"& on4)#") !)ara"#& "an a5e a a3or #!a"& onr#5 ana(een& an' !aen& "arer#5 ana(een& an' !aen& "are

A*era(e 'a&a are ue+ul a a (u#'e6 1u&A*era(e 'a&a are ue+ul a a (u#'e6 1u&

ula&ely, #n+oraon !er&a#n#n( &o &)eula&ely, #n+oraon !er&a#n#n( &o &)e#n'#*#'ual !aen& # all-#!or&an& 7#n'#*#'ual !aen& # all-#!or&an& 7 interindividualinterindividualvariability variability

In&ra#n'#*#'ual *ar#a1#l#&yIn&ra#n'#*#'ual *ar#a1#l#&y # (enerally u")# (enerally u")

aller &)an #n&er#n'#*#'ual *ar#a1#l#&yaller &)an #n&er#n'#*#'ual *ar#a1#l#&y

T)ere are &)ree a#n our"e o+ *ar#a1#l#&y #nT)ere are &)ree a#n our"e o+ *ar#a1#l#&y #n!)ara"o5#ne" o+ 'ru( an' "oneuen&ly!)ara"o5#ne" o+ 'ru( an' "oneuen&ly

!aen&0 re!one &o 'ru(!aen&0 re!one &o 'ru(


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INTRODUCTION...INTRODUCTION...


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8IOLOGICAL FACTORS8IOLOGICAL FACTORS9. A(e:9. A(e:T)e +a"&or &)a& a$e"& 'ru( a1or!on,T)e +a"&or &)a& a$e"& 'ru( a1or!on,

#n"lu'#n( (a&r#" !H, (a&r#" e!&y#n(, #n&enal#n"lu'#n( (a&r#" !H, (a&r#" e!&y#n(, #n&enal

ol#&y , an' 1loo' ;o4 ")an(e 4#&) a(eol#&y , an' 1loo' ;o4 ")an(e 4#&) a(e

T)u, #n &)e neona&e a "on'#on o+ a")lor)y'r#aT)u, #n &)e neona&e a "on'#on o+ a")lor)y'r#a

!er#& +or &)e


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS29. A(e29. A(e2

S5ele&al u"le a # alo u") re'u"e', an'S5ele&al u"le a # alo u") re'u"e', an'u"le "on&ra"on, 4)#") &en' &o !roo&e 1o&)u"le "on&ra"on, 4)#") &en' &o !roo&e 1o&)1loo' ;o4 an' !rea'#n( o+ an #n&rau"ularly1loo' ;o4 an' !rea'#n( o+ an #n&rau"ularlya'#n#&ere' 'ru(, are rela*ely +ee1lea'#n#&ere' 'ru(, are rela*ely +ee1le

An ele*a&e' (a&r#" !H, a 'elay #n (a&r#"An ele*a&e' (a&r#" !H, a 'elay #n (a&r#"e!&y#n(, an' 1o&) '##n#)e' #n&enal ol#&ye!&y#n(, an' 1o&) '##n#)e' #n&enal ol#&yan' 1loo' ;o4 are alo een #n &)e el'erlyan' 1loo' ;o4 are alo een #n &)e el'erly

D#$eren"e #n 'ru( a1or!on aon( a'ul&, &)eD#$eren"e #n 'ru( a1or!on aon( a'ul&, &)e*ery youn( an' &)e el'erly, are &)ere+ore e%!e"&e'*ery youn( an' &)e el'erly, are &)ere+ore e%!e"&e'

Generally, ")an(e #n ra&e ra&)er &)an #n e%&en&Generally, ")an(e #n ra&e ra&)er &)an #n e%&en&o+ a1or!on are +oun'o+ a1or!on are +oun'


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS29. A(e29. A(e2

T)ee ")an(e &en' &o 1e le a!!aren& #n &)eT)ee ")an(e &en' &o 1e le a!!aren& #n &)eel'erly &)an #n &)e *ery youn(el'erly &)an #n &)e *ery youn(

C)#l'ren o+&en a!!ear &o a1or1 'ru( aC)#l'ren o+&en a!!ear &o a1or1 'ru( a

"o!le&ely an', #+ any&)#n(, ore ra!#'ly &)an"o!le&ely an', #+ any&)#n(, ore ra!#'ly &)ana'ul&a'ul&

A""or'#n(ly, #n u1euen& "al"ulaon o+ 'oa(e,A""or'#n(ly, #n u1euen& "al"ulaon o+ 'oa(e,

e%&en& o+ a1or!on # aue' no& &o *ary 4#&) a(ee%&en& o+ a1or!on # aue' no& &o *ary 4#&) a(e

A a3or e%"e!on # +or oe


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS29. A(e29. A(e2Generally, !laa 1#n'#n( # lo4er #n neona&e &)anGenerally, !laa 1#n'#n( # lo4er #n neona&e &)ana'ul&a'ul&

Dur#n( a'ul&)oo' &)e *alue o+Dur#n( a'ul&)oo' &)e *alue o+ f f uu >+ra"on o+ un1oun'>+ra"on o+ un1oun''ru( #n !laa? rea#n un")an(e' or &en' &o ra#e +or'ru( #n !laa? rea#n un")an(e' or &en' &o ra#e +or&)oe 'ru( 1oun' &o al1u#n, &)e "on"en&raon o+&)oe 'ru( 1oun' &o al1u#n, &)e "on"en&raon o+4)#") +all l#()&ly 4#&) a'*an"#n( year4)#") +all l#()&ly 4#&) a'*an"#n( year

T)e ")an(e #n 1#n'#n( # (enerally &oo all, &oT)e ")an(e #n 1#n'#n( # (enerally &oo all, &o4arran& any "on#'eraon o+ 'oe a'3u&en&4arran& any "on#'eraon o+ 'oe a'3u&en&

Clearan"e, #+ noral#@e' +or 1o'y 4e#()&, # 'e!ree'Clearan"e, #+ noral#@e' +or 1o'y 4e#()&, # 'e!ree'

#n &)e neona&e, 1u& #n"reae ra!#'ly &o rea") a#n &)e neona&e, 1u& #n"reae ra!#'ly &o rea") aa%#u *alue a& on&), 4)en #& # alo& &4#"ea%#u *alue a& on&), 4)en #& # alo& &4#"e&)a& #n &)e a'ul&&)a& #n &)e a'ul& T)ere+ore, 4e#()& 7noral#@e' "learan"e +all 1u& llT)ere+ore, 4e#()& 7noral#@e' "learan"e +all 1u& ll

rea#n, &)rou()ou& ")#l')oo', "on#'era1ly a1o*e &)erea#n, &)rou()ou& ")#l')oo', "on#'era1ly a1o*e &)ea'ul& *aluea'ul& *alue


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS29. A(e29. A(e2T)e )al+ l#+e # )or&e& aroun' 9 year o+ a(e6 #& #T)e )al+ l#+e # )or&e& aroun' 9 year o+ a(e6 #& #lon(e& #n 1o&) ne41orn an' el'erly !aen&lon(e& #n 1o&) ne41orn an' el'erly !aen&

In !rea&ure ne41orn, &)e ur#nary e%"reon # e*enIn !rea&ure ne41orn, &)e ur#nary e%"reon # e*enore 'e!ree' !er 5#lo(ra o+ 1o'y 4e#()& &)an #n +ull-ore 'e!ree' !er 5#lo(ra o+ 1o'y 4e#()& &)an #n +ull-&er neona&e&er neona&e

Me&a1ol#" a"*#&y ay &a5e on&) &o a&ure, &)e eMe&a1ol#" a"*#&y ay &a5e on&) &o a&ure, &)e ereu#re' +or +ull a&uraon *ar#e 4#&) &)e en@yereu#re' +or +ull a&uraon *ar#e 4#&) &)e en@yey&ey&e

A 'e"reae #n un1oun' e&a1ol#" "learan"e #n &)eA 'e"reae #n un1oun' e&a1ol#" "learan"e #n &)e

el'erly !aen& )a 1een 'eon&ra&e' +or an #n"rea#n(el'erly !aen& )a 1een 'eon&ra&e' +or an #n"rea#n(nu1er o+ 'ru(, e!e"#ally, &)oe !r#n"#!ally 1y o%#'aonnu1er o+ 'ru(, e!e"#ally, &)oe !r#n"#!ally 1y o%#'aon T)ee ")an(e ay 1e ao"#a&e' #n !ar&, 4#&) &)eT)ee ")an(e ay 1e ao"#a&e' #n !ar&, 4#&) &)e'e"reae #n &)e #@e o+ &)e l#*er, a a !ro!oron o+ 1o'y'e"reae #n &)e #@e o+ &)e l#*er, a a !ro!oron o+ 1o'y4e#()&, +ro B. #n &)e youn( a'ul& &o 9. a& year4e#()&, +ro B. #n &)e youn( a'ul& &o 9. a& year

o+ a(eo+ a(e


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS2B. 8o'y e#()&:B. 8o'y e#()&:One a!e"& o+ a(#n( # 1o'y 4e#()&One a!e"& o+ a(#n( # 1o'y 4e#()&

e#()&, =. 5( a& 1#r&), #n"reae ra!#'ly #n ")#l')oo'e#()&, =. 5( a& 1#r&), #n"reae ra!#'ly #n ")#l')oo'an' a'ole"en"e an' &)en 'e"l#ne lo4ly #n &)e el'erlyan' a'ole"en"e an' &)en 'e"l#ne lo4ly #n &)e el'erly

A 1o'y 4a&er !a"e, u"le a, or(an 1loo' ;o4,A 1o'y 4a&er !a"e, u"le a, or(an 1loo' ;o4,

an' or(an +un"on are rela&e' &o 1o'y 4e#()&, &)ean' or(an +un"on are rela&e' &o 1o'y 4e#()&, &)e*olue o+ '#&r#1uon, "learan"e an' )en"e 'oa(e*olue o+ '#&r#1uon, "learan"e an' )en"e 'oa(ere(#en o+ 'ru( alo 'e!en' on 1o'y 4e#()&re(#en o+ 'ru( alo 'e!en' on 1o'y 4e#()&

Ho4e*er, a 4e#()& a'3u&en& # (enerally &)ou()&Ho4e*er, a 4e#()& a'3u&en& # (enerally &)ou()&

ne"eary only #+ &)e 4e#()& o+ an #n'#*#'ual '#$er 1yne"eary only #+ &)e 4e#()& o+ an #n'#*#'ual '#$er 1yore &)an = +ro &)e a*era(e a'ul& 4e#()& > 5(?ore &)an = +ro &)e a*era(e a'ul& 4e#()& > 5(?

In !ra""e, &)en, a'3u&en& +or 4e#()& are a'eIn !ra""e, &)en, a'3u&en& +or 4e#()& are a'eonly +or &)e ")#l' an' +or &)e a'ul& 4)o # all, &)#n,only +or &)e ")#l' an' +or &)e a'ul& 4)o # all, &)#n,

1#(, or o1ee1#(, or o1ee


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS2B. 8o'y e#()&:B. 8o'y e#()&:

A 'oe "orre"on u& 1e "on#'ere' +or &)#n an'A 'oe "orre"on u& 1e "on#'ere' +or &)#n an'o1ee !aen&o1ee !aen&

T)e '#$eren"e #n loa'#n( 'oe ay no& 1e a (rea&T)e '#$eren"e #n loa'#n( 'oe ay no& 1e a (rea&a an"#!a&e' +ro 1o'y 4e#()& alonea an"#!a&e' +ro 1o'y 4e#()& alone

8e"aue, '#&r#1uon (e& a(e-rela&e' ")an(e an'8e"aue, '#&r#1uon (e& a(e-rela&e' ")an(e an'u") 'e!en' on &)e !)y#"o")e#"al !ro!ere o+u") 'e!en' on &)e !)y#"o")e#"al !ro!ere o+&)e 'ru(&)e 'ru(

For e%a!le, '#(o%#n an' o&)er !olar 'ru( >4a&erFor e%a!le, '#(o%#n an' o&)er !olar 'ru( >4a&erolu1le? )o4 1e&&er "orrelaon 1e&4een un1oun'olu1le? )o4 1e&&er "orrelaon 1e&4een un1oun'*olue o+ '#&r#1uon >*olue o+ '#&r#1uon >V V uu? 4#&) lean 1o'y a,? 4#&) lean 1o'y a,

4)#") # ##lar #n o1ee an' a*era(e !eron o+ &)e4)#") # ##lar #n o1ee an' a*era(e !eron o+ &)eae )e#()& an' +rae, &)an 4#&) &o&al 1o'y 4e#()&ae )e#()& an' +rae, &)an 4#&) &o&al 1o'y 4e#()&


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS2B. 8o'y e#()&:B. 8o'y e#()&:

In "on&ra&, &o&al 1o'y 4e#()& ay 1e oreIn "on&ra&, &o&al 1o'y 4e#()& ay 1e orerele*an& +or a 'ru( &)a& # )#()ly l#!#' olu1lerele*an& +or a 'ru( &)a& # )#()ly l#!#' olu1le

T)ou() renal an' )e!a" +un"on are rela&e'T)ou() renal an' )e!a" +un"on are rela&e'&o 1o'y #@e, o1e#&y ay no& !ro'u"e a&o 1o'y #@e, o1e#&y ay no& !ro'u"e a"orre!on'#n( #n"reae #n )e!a" +un"on"orre!on'#n( #n"reae #n )e!a" +un"on

Coneuen&ly, &)e ue o+ &o&al 1o'y 4e#()& &oConeuen&ly, &)e ue o+ &o&al 1o'y 4e#()& &o'e&er#ne a 'ru( 'oa(e re(#en "oul' reul& #n'e&er#ne a 'ru( 'oa(e re(#en "oul' reul& #n

&o%#" e$e"& #+ &)e !aen& # (roly o1ee&o%#" e$e"& #+ &)e !aen& # (roly o1ee

T)u, &)ou() any 'ru( 'oe are 1ae' on &)eT)u, &)ou() any 'ru( 'oe are 1ae' on &)e1o'y 4e#()& o+ &)e !aen& >e%!ree' a (5(?,1o'y 4e#()& o+ &)e !aen& >e%!ree' a (5(?,

&)e #n;uen"e o+ o1e#&y or alnour#)en& # no&&)e #n;uen"e o+ o1e#&y or alnour#)en& # no&al4ay "on#'ere'al4ay "on#'ere'


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS2=. Gen'er:=. Gen'er:

Gene" an' !)y#olo(#"al '#$eren"e 1e&4een enGene" an' !)y#olo(#"al '#$eren"e 1e&4een enan' 4oen "an #n;uen"e 1o&) PK an' PDan' 4oen "an #n;uen"e 1o&) PK an' PD

For e%a!le, any (ene on &)e Y ")roooe,For e%a!le, any (ene on &)e Y ")roooe,4)#") are e%!ree' only #n ale, )a*e no4)#") are e%!ree' only #n ale, )a*e no

"oun&er!ar& on &)e ")roooe"oun&er!ar& on &)e ")roooe

T)e Y ")roooe )a (ene #n*ol*e' #n 1a#"T)e Y ")roooe )a (ene #n*ol*e' #n 1a#""ellular +un"on an' oe (ene on &)e "ellular +un"on an' oe (ene on &)e

")roooe are e%!ree' a& )#()er le*el #n +eale")roooe are e%!ree' a& )#()er le*el #n +eale

Gene e%!re#on an' re(ulaon are l#5ely &o 1eGene e%!re#on an' re(ulaon are l#5ely &o 1e#n;uen"e' 1y )oronal '#$eren"e 1e&4een ale#n;uen"e' 1y )oronal '#$eren"e 1e&4een alean' +ealean' +eale


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS2=. Gen'er2=. Gen'er2

Geno#" #!r#nn(, 1o'y #@e, or(an #@e, 1o'yGeno#" #!r#nn(, 1o'y #@e, or(an #@e, 1o'y+a&, ADME "an alo a$e"& !)ara"olo(#"al ou&"oe+a&, ADME "an alo a$e"& !)ara"olo(#"al ou&"oe

O&)er +a"&or u") a (a&ro#n&enal &ran#& e,O&)er +a"&or u") a (a&ro#n&enal &ran#& e,l#*er en@ye +un"on an' ur#nary "rean#nel#*er en@ye +un"on an' ur#nary "rean#ne"learan"e are #n;uen"e' 1y 1o&) a(e an' e%"learan"e are #n;uen"e' 1y 1o&) a(e an' e%

A"ro &)e !a&) o+ a 4oan0 l#+e #& # ne"eary &oA"ro &)e !a&) o+ a 4oan0 l#+e #& # ne"eary &o"on#'er &)e &a(e o+ o*ar#an +un"on &o a!!re"#a&e"on#'er &)e &a(e o+ o*ar#an +un"on &o a!!re"#a&e

&)e !o&enal +or 'ru(, e%, an' a(e #n&era"on a&)e !o&enal +or 'ru(, e%, an' a(e #n&era"on a&)ey #n;uen"e raonal 'ru( &)era!y&)ey #n;uen"e raonal 'ru( &)era!y

Ue o+ oral "on&ra"e!*e an' )oronal ")an(eUe o+ oral "on&ra"e!*e an' )oronal ")an(e

4)#") o""ur &)rou()ou& &)e en&rual "y"le4)#") o""ur &)rou()ou& &)e en&rual "y"le#n;uen"e !)ara"olo(#"al reul&#n;uen"e !)ara"olo(#"al reul&


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS2=. Gen'er2=. Gen'er2Ne"eary "on#'eraon 'ur#n( !re(nan"y areNe"eary "on#'eraon 'ur#n( !re(nan"y areal&eraon #n 1o'y "o!o#on, "ar'#a" ou&!u&,al&eraon #n 1o'y "o!o#on, "ar'#a" ou&!u&,

!ulonary an' renal +un"on a 4ell a ")an(e #n!ulonary an' renal +un"on a 4ell a ")an(e #n#une an' (a&ro#n&enal y&e#une an' (a&ro#n&enal y&e

In eno!aue, &)e o*ar#e, u&eru, ur#nary &ra"&,In eno!aue, &)e o*ar#e, u&eru, ur#nary &ra"&,)y!o&)alau, "ar'#o*a"ular y&e, an' l#*er are)y!o&)alau, "ar'#o*a"ular y&e, an' l#*er are

oe o+ &)e ue, or(an or y&e 4)#") areoe o+ &)e ue, or(an or y&e 4)#") areal&ere' 1y &)e lo o+ e&ro(en, an'ro(en, an'al&ere' 1y &)e lo o+ e&ro(en, an'ro(en, an'!ro(e&a(en!ro(e&a(en

T)ee )oronal ")an(e are alo ao"#a&e' 4#&) &)eT)ee )oronal ")an(e are alo ao"#a&e' 4#&) &)ee%!re#on o+ '#$eren& '#eae a+&er eno!auee%!re#on o+ '#$eren& '#eae a+&er eno!aue

Se% '#$eren"e #n"lu'e &)e o1er*aon &)a& #n anySe% '#$eren"e #n"lu'e &)e o1er*aon &)a& #n any'e*elo!e' "oun&r#e 4oen &a5e ore e'#"aon,'e*elo!e' "oun&r#e 4oen &a5e ore e'#"aon,"rean( &)e !o&enal +or a'*ere e$e"& 1ae' on 'ru("rean( &)e !o&enal +or a'*ere e$e"& 1ae' on 'ru(#n&era"on, &)ey a!!ear ore en#*e &o a'*ere#n&era"on, &)ey a!!ear ore en#*e &o a'*ere

e*en&, an' ay 1e o*er'oe' ore +reuen&lye*en&, an' ay 1e o*er'oe' ore +reuen&ly


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Buserelin for endometriosis (300 µg intra nasally 3times

a day) or for prostate cancer (200µg intra nasally 6


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8IOLOGICAL FACTORS28IOLOGICAL FACTORS2. Gene":. Gene":Gene" !olyor!)# &)a& lea' &o &)e !ro'u"on o+Gene" !olyor!)# &)a& lea' &o &)e !ro'u"on o+

#oen@ye 4#&)#oen@ye 4#&) re'u"e're'u"e' oror no a"*#&y o+no a"*#&y o+ &o&o ul!leul!le"o!#e o+"o!#e o+ an en@ye 4#&)an en@ye 4#&) )#() a"*#&y)#() a"*#&y a5e a a3ora5e a a3or"on&r#1uon &o &)e *ar#a1#l#&y #n &)e 'oe reu#reen&"on&r#1uon &o &)e *ar#a1#l#&y #n &)e 'oe reu#reen&o+ 'ru( &)a& el##na&e' 1y )e!a" e&a1ol#o+ 'ru( &)a& el##na&e' 1y )e!a" e&a1ol#

Cy&o")roe P >CYP ? en@ye, P 7Cy&o")roe P >CYP ? en@ye, P 7(ly"o!ro&e#n are #n"rea#n(ly 1e#n( re"o(n#@e' +or(ly"o!ro&e#n are #n"rea#n(ly 1e#n( re"o(n#@e' +or&)e#r #!or&an"e &o !)ara"o5#ne" *ar#a1#l#&y&)e#r #!or&an"e &o !)ara"o5#ne" *ar#a1#l#&y

Mo& o+ &)ee (ene" '#$eren"e are "o!le% an' areMo& o+ &)ee (ene" '#$eren"e are "o!le% an' are'#"ul& &o 'e&er#ne 4#&) any 'e(ree o+ "er&a#n&y6 1u&'#"ul& &o 'e&er#ne 4#&) any 'e(ree o+ "er&a#n&y6 1u&

a +e4 (ene" '#$eren"e are 4ell 'o"uen&e'a +e4 (ene" '#$eren"e are 4ell 'o"uen&e'>o%#'aon, S- e&)ylaon, an' a"e&ylaon?>o%#'aon, S- e&)ylaon, an' a"e&ylaon?

In +u&ure, (ene" "reen#n( >!)eno&y!#n(? ay 1eIn +u&ure, (ene" "reen#n( >!)eno&y!#n(? ay 1e'one &o #n'#*#'ual !aen& &o 'e#(n &)e 'oe o+ a'one &o #n'#*#'ual !aen& &o 'e#(n &)e 'oe o+ a

'ru('ru(


21/34

8IOLOGICAL FACTORS28IOLOGICAL FACTORS2. Gene"2. Gene"2

Probe drugs approved by US !" for geneticp#enotyping

$mepra%ole & Pantopra%ole (P#enotyping for'P2'*)


22/34

8IOLOGICAL FACTORS28IOLOGICAL FACTORS2. Gene"2. Gene"2


23/34

8IOLOGICAL FACTORS28IOLOGICAL FACTORS2. D#eae Con'#on:. D#eae Con'#on:

D#eae # a a3or our"e o+ *ar#a1#l#&y #n 'ru(D#eae # a a3or our"e o+ *ar#a1#l#&y #n 'ru(re!onere!one

T)e PK an' PD o+ oe 'ru( )a*e 1een )o4nT)e PK an' PD o+ oe 'ru( )a*e 1een )o4n

&o 1e #n;uen"e' 1y &)e !reen"e o+ "on"urren&&o 1e #n;uen"e' 1y &)e !reen"e o+ "on"urren&'#eae o&)er &)an &)e one +or 4)#") a 'ru( #'#eae o&)er &)an &)e one +or 4)#") a 'ru( #ue'ue'

T)ere are alo o""a#on 4)en &)eT)ere are alo o""a#on 4)en &)e

!)ara"o5#ne" o+ a 'ru( # al&ere' #n &)e!)ara"o5#ne" o+ a 'ru( # al&ere' #n &)e'#eae +or 4)#") #& # ue''#eae +or 4)#") #& # ue'

D#eae o+ &)e 5#'ney, l#*er, "ar'#o *a"ularD#eae o+ &)e 5#'ney, l#*er, "ar'#o *a"ulary&e, re!#ra&ory y&e, (a&ro#n&enaly&e, re!#ra&ory y&e, (a&ro#n&enal

y&e an' en'o"r#ne y&e are &)e a3ory&e an' en'o"r#ne y&e are &)e a3or"aue &)a& 4arran& #n'#*#'ual#@e' 'ru( &)era!y"aue &)a& 4arran& #n'#*#'ual#@e' 'ru( &)era!y


24/34

8IOLOGICAL FACTORS28IOLOGICAL FACTORS2. D#eae Con'#on2. D#eae Con'#on2CONDITIO

N

DRUG O8SERATIO

N

ARIATION

IN

COMMENTS

PK PD

HEPATIC DISEASES

C#rr)o# T)eo!)yll#n

e

Slo4er +all #n

!laa"on"en&raon

- Clearan"ere'u"e'.Re'u"e &)e'oa(e &oa*o#' &o%#"#&y

A"u&e *#ral)e!a

ar+ar#n E%"e#*ean"oa(ulan&

re!one

- Re'u"e'oa(e &o

leen r#5 o+)eorr)a(e

RENAL DISEASES

Ure#a Gen&ay"#n In"reae'&o%#"#&y 4#&)uual 'oa(e

- Renal"learan"e'##n#)e'6

re'u"e'oa(e &o


25/34


N

DRUG O8SERATIO

N

ARIATION

IN

COMMENTS

PK PD

CARDIOASCULAR DISEASE

Con(e*e

Car'#a"Fa#lure

l#'o"a#ne Ele*a&e'

!laa"on"en&raona+&er uual'oa(e

- Clearan"e an'

' re'u"e'.Re'u"e &)e'oa(e &oleen&o%#"#&y

GASTROINTESTINAL DISEASES

Cel#a"D#eae

Fu#'#" A"#' Ele*a&e'!laa"on"en&raona+&er uual'oa(e

- 8A #n"reae'an' Clearan"e'##n#)e'

Cro)n0

D#eae

Pro!ranolol Ele*a&e'

!laa"on"en&raon

NS In"reae'

!laa1#n'#n(,


26/34

8IOLOGICAL FACTORS28IOLOGICAL FACTORS2. D#eae Con'#on2. D#eae Con'#on2

CONDITION

DRUG O8SERATION

ARIATIONIN

COMMENTS

PK PD

RESPIRATORY DISEASES

A&)a Tol1u&a#'e

More ra!#' +all#n !laa"on"en&raon

- T)era!eu""oneuen"eun"er&a#n

E!)yea Mor!)#ne In"reae'en#*#&y &ore!#ra&ory'e!rean&e$e"&

NS NS Re'u"e 'oe&o '##n#)r#5 o+re!#ra&ory"o!l#"aon

Cy"


27/34


N

DRUG O8SERATION ARIATION

IN

COMMENTS

PK PD

ENDOCRINE DISEASE

T)yro#'

'#eae

D#(o%#n D##n#)e'

re!one #n )y!er&)yro#'#6#n"reae're!one #ny%e'ea

- A'3u& 'oa(ea""or'#n( &o&)yro#'a"*#&y

OTHER

Fe*er u#n#ne Plaa"on"en&raon o+'ru( ele*a&e', o+e&a1ol#&e'e!ree', a+&eruual 'oa(e

NS I!a#re'e&a1ol#u!e"&e'6ay nee' &ore'u"e 'oe#n e*ere+e1r#le &a&e

. /stablis#ed source of ariability-. 1o evidence t#at variability is increased due to

disease1S 1ot Studied


28/34

ENIRONMENTAL FACTORSENIRONMENTAL FACTORS9. Dru( In&era"on:9. Dru( In&era"on:

Many o+ &)e "l#n#"ally #(n#


29/34

ENIRONMENTAL FACTORSENIRONMENTAL FACTORS9. Dru( In&era"on29. Dru( In&era"on2

A1or!on:A1or!on:

S&u'#e )a*e 'eon&ra&e' &)e #!or&an"e o+S&u'#e )a*e 'eon&ra&e' &)e #!or&an"e o+#n&enal CYP=A an' P 7 (ly"o!ro&e#n #n 'ru(#n&enal CYP=A an' P 7 (ly"o!ro&e#n #n 'ru(

a1or!ona1or!on

In'u"on o+ &)ee e")an# 1y r#+a!#"#nIn'u"on o+ &)ee e")an# 1y r#+a!#"#nan' 1y S& Jo)n0 4or& )a*e 1een )o4n &oan' 1y S& Jo)n0 4or& )a*e 1een )o4n &ore'u"e &)e 8A o+ D#(o%#nre'u"e &)e 8A o+ D#(o%#n

A1or!on "an alo 1e al&ere' 1y 'ru(A1or!on "an alo 1e al&ere' 1y 'ru(#n&era"on 4#&)#n &)e (u& &)a& reul& +ro#n&era"on 4#&)#n &)e (u& &)a& reul& +ro1#n'#n( &o o&)er 'ru(, u") a ")ole&yra#ne1#n'#n( &o o&)er 'ru(, u") a ")ole&yra#neor an&a"#', or &o en&eral +ee', a #n &)e "ae o+or an&a"#', or &o en&eral +ee', a #n &)e "ae o+

P)eny&o#nP)eny&o#n


30/34

ENIRONMENTAL FACTORSENIRONMENTAL FACTORS9. Dru( In&era"on29. Dru( In&era"on2

D#&r#1uon:D#&r#1uon:Dru( '#&r#1uon "an 1e al&ere' 1y #n&era"onDru( '#&r#1uon "an 1e al&ere' 1y #n&era"on&)a& "aue '#!la"een& +ro !laa !ro&e#n&)a& "aue '#!la"een& +ro !laa !ro&e#n1#n'#n(1#n'#n(

8u&, &)ee 'o no& norally al&er a#n&enan"e8u&, &)ee 'o no& norally al&er a#n&enan"e'oe reu#reen& unle &)ere # alo a re'u"on'oe reu#reen& unle &)ere # alo a re'u"on#n &)e "learan"e o+ un1oun' 'ru(#n &)e "learan"e o+ un1oun' 'ru(

Me&a1ol#:Me&a1ol#:Me&a1ol# "an 1e al&ere' 1y en@ye #n'u"onMe&a1ol# "an 1e al&ere' 1y en@ye #n'u"onor #n)#1#onor #n)#1#on

Due &o 4#'e *ar#a1#l#&y #n en@ye a"*#&y, &)eDue &o 4#'e *ar#a1#l#&y #n en@ye a"*#&y, &)e

"l#n#"al #(n#


31/34

ENIRONMENTAL FACTORSENIRONMENTAL FACTORS9. Dru( In&era"on29. Dru( In&era"on2Me&a1ol#2Me&a1ol#2T)ee #n&era"on are o+&en 'oe-'e!en'en& an'T)ee #n&era"on are o+&en 'oe-'e!en'en& an'&)e e"ale o+ &)e o$e& an' one& o+ &)e e$e"&&)e e"ale o+ &)e o$e& an' one& o+ &)e e$e"&'e!en' no& only on &)e PK o+ &4o >or ore? 'ru('e!en' no& only on &)e PK o+ &4o >or ore? 'ru("on"erne', 1u& alo &)e #oen@ye>? re!on#1le +or"on"erne', 1u& alo &)e #oen@ye>? re!on#1le +or&)e#r e&a1ol#&)e#r e&a1ol#

E%"reon:E%"reon:Pro1ene"#' re'u"e &)e renal e%"reon o+ anyPro1ene"#' re'u"e &)e renal e%"reon o+ anyan#o" 1y "o!en( +or an#on e"reonan#o" 1y "o!en( +or an#on e"reon&ran!or& e")an#&ran!or& e")an#

C)an(e #n 1#l#ary e"reon an' en&ero-)e!a"C)an(e #n 1#l#ary e"reon an' en&ero-)e!a""#r"ulaon "an alo !lay a role"#r"ulaon "an alo !lay a role

For e%a!le, Pen#"#ll#n "an #!a#r &)e re"#r"ulaonFor e%a!le, Pen#"#ll#n "an #!a#r &)e re"#r"ulaon

o+ oral "on&ra"e!*e 1y al&er#n( &)e 1a"&er#al ;orao+ oral "on&ra"e!*e 1y al&er#n( &)e 1a"&er#al ;orao+ &)e (u&o+ &)e (u&


32/34

ENIRONMENTAL FACTORSENIRONMENTAL FACTORSB. O&)er En*#ronen&al Fa"&or:B. O&)er En*#ronen&al Fa"&or:D#e&, "l#a&e, o5#n(, al"o)ol, 'ru(, !ollu&an&D#e&, "l#a&e, o5#n(, al"o)ol, 'ru(, !ollu&an&ay "aue 4#'e *ar#aon #n 'ru( re!one 4#&)#nay "aue 4#'e *ar#aon #n 'ru( re!one 4#&)#nan #n'#*#'ualan #n'#*#'ual

Se*eral o+ &)ee +a"&or "an o!era&eSe*eral o+ &)ee +a"&or "an o!era&e#ul&aneouly #n &)e ae #n'#*#'ual, &)u#ul&aneouly #n &)e ae #n'#*#'ual, &)u

a$e"n( &)e !ro"ee o+ ADME an' re"e!&ora$e"n( &)e !ro"ee o+ ADME an' re"e!&or#n&era"on #n '#$eren& 4ay an' &o '#$erenn&era"on #n '#$eren& 4ay an' &o '#$eren&'e(ree'e(ree

S&u'#e "o!ar#n( &)e e&a1ol# o+ An!yr#neS&u'#e "o!ar#n( &)e e&a1ol# o+ An!yr#ne

1e&4een A#an In'#an #n rural In'#an *#lla(e an'1e&4een A#an In'#an #n rural In'#an *#lla(e an'In'#an ##(ran& #n En(lan' 'eon&ra&e' &)a& aIn'#an ##(ran& #n En(lan' 'eon&ra&e' &)a& a##(ran& a'o!&e' &)e l#+e&yle an' '#e&ary )a1#&##(ran& a'o!&e' &)e l#+e&yle an' '#e&ary )a1#&o+ &)e 8r#), &)e#r 'ru( e&a1ol# a""elera&e'o+ &)e 8r#), &)e#r 'ru( e&a1ol# a""elera&e'

L#()&-5#nne' #n'#*#'ual are u13e"& &o 'ru(-L#()&-5#nne' #n'#*#'ual are u13e"& &o 'ru(-#n'u"e' !)o&o&o%#"#&y a+&er #n(en( "er&a#n 'ru(#n'u"e' !)o&o&o%#"#&y a+&er #n(en( "er&a#n 'ru(


33/34

CULTURAL FACTORSCULTURAL FACTORS

Cul&ural or !y")oo"#al +a"&or, u") a &)eCul&ural or !y")oo"#al +a"&or, u") a &)e

a&&u'e an' 1el#e+ o+ an e&)n#" (rou!, aya&&u'e an' 1el#e+ o+ an e&)n#" (rou!, aya$e"& &)e e$e"*ene o+, or a')eren"e &o, aa$e"& &)e e$e"*ene o+, or a')eren"e &o, a!ar"ular 'ru( &)era!y!ar"ular 'ru( &)era!y

S&u'#e )a*e "on#&en&ly )o4n &)a& A+r#"an-S&u'#e )a*e "on#&en&ly )o4n &)a& A+r#"an-Aer#"an !aen& are ore l#5ely &o 1e o*erAer#"an !aen& are ore l#5ely &o 1e o*er'#a(noe' a )a*#n( a !y")o" #llne an' are'#a(noe' a )a*#n( a !y")o" #llne an' areore l#5ely &o 1e &rea&e' 4#&) neurole!"ore l#5ely &o 1e &rea&e' 4#&) neurole!"re(ar'le o+ '#a(no#re(ar'le o+ '#a(no#

A+r#"an-Aer#"an are alo ore l#5ely &o 1eA+r#"an-Aer#"an are alo ore l#5ely &o 1e!la"e' on #!lan&e' or !er#o'#"ally #n3e"&e'!la"e' on #!lan&e' or !er#o'#"ally #n3e"&e'ra&)er &)an oral e'#"aon, re;e"n(ra&)er &)an oral e'#"aon, re;e"n(!)y#"#an0 "on"ern a1ou& a')eren"e!)y#"#an0 "on"ern a1ou& a')eren"e


34/34

CONCLUSIONSCONCLUSIONS

Heal&) "are !ro*#'er )oul' (#*e #n'#*#'ual#@e'Heal&) "are !ro*#'er )oul' (#*e #n'#*#'ual#@e'

&rea&en& &o ea") !aen& an' re#& &)e &e!&aon&rea&en& &o ea") !aen& an' re#& &)e &e!&aon&o a!!ly "oo51oo5Q 'ru( &)era!y &)a& 'oe no& &a5e&o a!!ly "oo51oo5Q 'ru( &)era!y &)a& 'oe no& &a5e#n&o a""oun& *ar#aon aon( #n'#*#'ual !aen&#n&o a""oun& *ar#aon aon( #n'#*#'ual !aen&

For &)e !ra""#n( !)y#"#an, ea") !aen&For &)e !ra""#n( !)y#"#an, ea") !aen&

re!reen& a un#ue an' 'yna#" #n&era"on aon(re!reen& a un#ue an' 'yna#" #n&era"on aon('e&er#nan& &)a& are 1o&) (ene" an''e&er#nan& &)a& are 1o&) (ene" an'en*#ronen&alen*#ronen&al

I& # #!era*e &o #n'#*#'ual#@e &)era!y 4#&)I& # #!era*e &o #n'#*#'ual#@e &)era!y 4#&)re!e"& &o &)e a!!ro!r#a&e ")o#"e o+ 1o&) 'ru( an're!e"& &o &)e a!!ro!r#a&e ")o#"e o+ 1o&) 'ru( an''oe'oe

A Cl#n#"al !)ara"#& 4#&) a'eua&eA Cl#n#"al !)ara"#& 4#&) a'eua&e!)ara"o5#ne" 1a"5(roun' "an !lay a *#&al role #n!)ara"o5#ne" 1a"5(roun' "an !lay a *#&al role #n)el!#n( &)e !)y#"#an +or #n'#*#'ual#@#n( 'ru()el!#n( &)e !)y#"#an +or #n'#*#'ual#@#n( 'ru(

&)era!y&)era!y

Documents

Individualization of drug dosage regimen.ppt