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Pharmaceuticals and Medical Devices
Safety Information No.219

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No. $B45 $B#1F|EjM?NL(B
$BEjM?4|4V(B		 $BI{:nMQ(B $BHw9M(B
$B@-(B $B!&(B
$BG/Np(B		 $B;HMQM}M3(B
$B!J9gJ;>I!K(B		 $B7P2a5Z$S=hCV(B
1 $B=w(B
60$BBe(B		 $B>eIt>C2=4I(BX$B@~B$1F(B
$B!J$J$7!K(B		 289g
$B#1F|4V(B		 $B%"%J%U%#%i%-%7!<%7%g%C%/(B
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$BEj!!M?!!F|(B $B8!?G0_F);k$N$?$a!$K\:^5Z$SJ;MQLt$rI~MQ!#(B
$BEjM?(B30$BJ,8e(B $BA4?HH/@V!$H/4@!$0-?4$,H/8=!#(B
$BEjM?#1;~4V8e(B $BMh1!!#<}=L4|7l05(B64mmHg$B!$%7%g%C%/>uBV$H?GCG!#(B
$BE@E)!JJd1U(B500mL$B!$%j%s;@%Y%?%a%?%>%s%J%H%j%&%`#4(Bmg$B!$(BdL-$B%^%l%$%s;@%/%m%k%U%'%K%i%_%s(B10mg$B!K$K$F!$>I>u2~A1798~!#%Y%?%a%?%>%s(B1.5mg$B!$1v;@%*%m%Q%?%8%s#5(Bmg$B$r7P8}EjM?!#=y!9$K>I>u2~A1!#(B
$BEjM?#3;~4V8e(B $BFHJb$G5"Bp!#(B
$BEjM?#1F|8e(B $B7P2a4Q;!Mh1!!#H/@V!$H/4@0[>o$OG'$a$:!#(B
$BEjM?(B13$BF|8e(B $B7P2a4Q;!Mh1!!#<+3P>I>u>C<:!#(B
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$BNW>28!::CM(B
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$B<}=L4|7l05!J(BmmHg$B!K(B 64 136 144 112
$B3HD%4|7l05!J(BmmHg$B!K(B $B!=(B 72 84 74
$BGr7l5e?t!J(B/mm3$B!K(B $B!=(B 13000 $B!=(B $B!=(B
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No. $B45 $B#1F|EjM?NL(B
$BEjM?4|4V(B		 $BI{:nMQ(B $BHw9M(B
$B@-(B $B!&(B
$BG/Np(B		 $B;HMQM}M3(B
$B!J9gJ;>I!K(B		 $B7P2a5Z$S=hCV(B
2 $B=w(B
30$BBe(B		 $B>eIt>C2=4I(BX$B@~B$1F(B
$B!J$J$7!K(B		 400g
$B#1F|4V(B		 $B%"%J%U%#%i%-%7!<%7%g%C%/(B
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$BEj!!M?!!F|(B $B?&>l8!?G$K$F!$K\:^!$C:;@?eAG%J%H%j%&%`!&
$BEjM?#1;~4V8e(B $BptItH/@V?>$K5$$E$/!#2l$KLa$C$?$,!$BN44!$;M;h$K!$<~0O$,H/@V$7$?KDN4?>$rG'$a$?!#(B
$BEjM?#3;~4V8e(B $B8F5[6l!$Dc7l05H/:n$rG'$a!$Ev1!$r
$BEjM?#3;~4V(B10$BJ,8e(B $B5uC&>uBV$G!$5^@-%"%l%k%.!<>I$N?GCG$GF~1!!#F~1!;~!$7l05!$L.Go?(CNITG=!#A4?H@-KDN4?>$rG'$a$?!#0U<1$OL@NF$G$"$k$,!$8F5[6l$rAJ$($k!#(BD.I.V.$B3NJ]$7!$%3%O%/;@%R%I%m%3%k%A%>%s%J%H%j%&%`(B500mg$B!\%0%j%A%k%j%A%s!&%0%j%7%s!&%7%9%F%$%sG[9g:^(B20mL$B$rE@E)@ECm!#(B
$BEjM?#3;~4V(B15$BJ,8e(B $B7l05(B70mmHg$B0J>e$K>e>:!#L.Go?(CN2DG=$H$J$C$?!#(B
$BEjM?#6;~4V8e(B $BKDN4?>$O>CB`798~!#0U<1L@NF!#8F5[6l>C<:!#(B
$BEjM?#1F|8e(B $BD+?)$r?)$7!$%Y%?%a%?%>%s!&(Bd-$B%^%l%$%s;@%/%m%k%U%'%K%i%_%sG[9g:^$NFbI~$b3+;O$5$l!$IB>u0BDj$77Z2wB`1!$H$J$C$?!#$=$N8e2sI|!#(B
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No. $B45 $B#1F|EjM?NL(B
$BEjM?4|4V(B		 $BI{:nMQ(B $BHw9M(B
$B@-(B $B!&(B
$BG/Np(B		 $B;HMQM}M3(B
$B!J9gJ;>I!K(B		 $B7P2a5Z$S=hCV(B
3 $BCK(B
70$BBe(B		 $B>eIt>C2=4I(BX$B@~B$1F(B
$B!J?)M_8:B`!K(B		 394.4g
$B#1F|4V(B		 $BJ"Kl1j(B
$BEj!!M?!!A0(B $B?);WIT?6$"$j!#(B
$BEj!!M?!!F|(B $B0eNE5!4X(BA$B$K$F>eIt>C2=4IF);k$r$B5"Bp8e!$J"DK!$K\:^$NSREG$N$?$a!$0eNE5!4X(BA$B$KF~1!!#(B
$BEjM?#1F|8e(B $BK3G"!$7l05Dc2<$,$_$i$l$?$?$a!$0eNE5!4X(BB$B$KHBAw$5$l!$D>$A$K6[5^3+J"!$9-HO0O0_@Z=|!J(BB-2$B:F7z!K!$(BBraun$BJ-9g!$6uD2ItJ,@Z=|=Q$,;\9T$5$l$?!#=Q8e!$%(%s%I%H%-%7%s5[CeNEK!$N;\9T$K$h$j!$7l05$O=y!9$K2~A1$7MxG"$rF@$?!#(B
$BEjM?(B33$BF|8e(B $BB`1!!#(B
$B4k6HJs9p(B
$BNW>28!::CM(B
$B!!(B $BEjM?#1F|8e(B
$BGr7l5e?t!J(B/mm3$B!K(B 4700
BUN$B!J(Bmg/dL$B!K(B 40.3
Cr$B!J(Bmg/dL$B!K(B 2.14
CRP$B!J(Bmg/dL$B!K(B 20.54
PT$B!J!s!K(B 48.4
APTT$B!JIC!K(B 33.8
$B%U%#%V%j%N%2%s!J(Bmg/dL$B!K(B 483
$BJ;MQLt!'C:;@?eAG%J%H%j%&%`!&



No. $B45 $B#1F|EjM?NL(B
$BEjM?4|4V(B		 $BI{:nMQ(B $BHw9M(B
$B@-(B $B!&(B
$BG/Np(B		 $B;HMQM}M3(B
$B!J9gJ;>I!K(B		 $B7P2a5Z$S=hCV(B
4 $B=w(B
70$BBe(B		 $B>eIt>C2=4I(BX$B@~B$1F(B
$B!J$J$7!K(B		 280g
$B#1F|4V(B		 $BD24I@|9&!$J"Kl1j(B
$B@8Mh7r9/(B
$BEj!!M?!!F|(B $B7r9/?GCG$K$FK\:^I~MQ!#8!::8e!$4K2<:^!J%;%s%J%(%-%9!KFbI~$9$k$bGSJX$J$7!#(B
$BEjM?#1F|8e(B $BMI>u$J$7!#J"It(BX$B@~;#1F$K$F%P%j%&%`JX$N;DB8$"$j!#%P%j%&%`JX$K$h$kD2JD:I$H?GCG$5$l!$%0%j%;%j%s^1D2#22s;\9T$7$?$,H?1~JX$J$7!#$=$N8e!$Hy29Er$K$F@vD2$9$k$bH?1~$J$7!#7P2a4Q;!$N$?$aF~1!!#(B
$BEjM?#2F|8e(B $BAaD+!$J"DKA}6/$7$?$?$aJ"It(BX$B@~;#1F;\9T$7$?$H$3$m!$9|HWFb$K%P%j%&%`$NCyN1$"$j!#D>D2@|9&$H?GCG!#6[5^D2A0JI$K(B2.5cm$BBg$N@|9&It$"$j!#D>D2@|9&ItJD:?5Z$S2#9T7kD2$K$F?M9)fjLgB$@_=Q;\9T!#(B
$BEjM?#2F|8e0J9_(B $B=Q8e!$GT7l>I@-%7%g%C%/$H$J$k$b!$J]B8E*<#NE$K$F7Z2w!#B`1!!#(B
$BEjM?(B66$BF|8e(B $B2sI|!#(B
$B4k6HJs9p(B
$BNW>28!::CM(B
$B!!(B $BEjM?F|(B $BEjM?#2F|8e(B
$B!J 		$BEjM?#2F|8e(B
$B!J 		$BEjM?#3F|8e(B $BEjM?#6F|8e(B
$B@V7l5e?t!J!_(B104/mm3$B!K(B 427 398 414 360 357
$B%X%b%0%m%S%s!J(Bg/dL$B!K(B 13.0 12.1 12.7 11.2 10.9
$B%X%^%H%/%j%C%H!J!s!K(B 41.5 37.2 39.2 33.8 32.7
$BGr7l5e?t!J(B/mm3$B!K(B 4200 7000 1600 11100 6700
CRP$B!J(Bmg/dL$B!K(B 0.05 0.0 $B!=(B 30.6 9.4
$BJ;MQLt!'C:;@?eAG%J%H%j%&%`!&


$B!Z(B2$B![(B $B%j%s;@%U%k%@%i%S%s(B

$BHNGdL>!J2q!K(B $B%U%k%@%i@ECmMQ(B50mg$B!JF|K\%7%(!<%j%s%0!K(B
$BLt8zJ,N`Ey(B $BBe
$B8zG=8z2L(B $BIO7lKt$O7l>.HD8:>/>I$rH<$&K}@-%j%s%Q@-Gr7lIB(B


$B!T(B$B;HMQ>e$NCm0U(B$B!J2<@~ItDI2C2~D{ItJ,!K!U(B

$B!NI{:nMQ(B
$B!J=EBg$JI{:nMQ!K!O(B		 $B<+8JLH1V@-7l>.HD8:>/>I(B$B!'<+8JLH1V@-7l>.HD8:>/>I$,$"$i$o$l$k$3$H$,$"$k$N$G!$4Q;!$r==J,$K9T$$!$0[>o$,G'$a$i$l$?>l9g$K$OEjM?$rCf;_$9$k$J$I!$E,@Z$J=hCV$r9T$&$3$H!#(B
$B@V2j5eat(B$B!'@V2j5eat$,$"$i$o$l$k$3$H$,$"$k$N$G!$4Q;!$r==J,$K9T$$!$0[>o$,G'$a$i$l$?>l9g$K$OEjM?$rCf;_$9$k$J$I!$E,@Z$J=hCV$r9T$&$3$H!#(B
$B!R;2!!!!!!9M!S(B $B4k6HJs9p(B
$BHNGd3+;O8e!JLs#5G/4V!K$N4XO"I{:nMQJs9p?t(B
$B!J!V0x2L4X78$,H]Dj$G$-$k$b$N!W0J30$N$b$N$G!$!V0x2L4X78$,ITL@$J$b$N!W$b4^$`!#!K(B
$B!&<+8JLH1V@-7l>.HD8:>/>I!'#4Nc!J$&$A;`K4#0Nc!K(B
$B!&@V2j5eat!'#5Nc!J$&$A;`K4#0Nc!K(B
$B4XO"4k6H$,?d7W$7$?$*$*$h$=$NG/4V;HMQ



$B>INc$N35MW(B

No. $B45 $B#1F|EjM?NL(B
$BEjM?4|4V(B		 $BI{:nMQ(B $BHw9M(B
$B@-(B $B!&(B
$BG/Np(B		 $B;HMQM}M3(B
$B!J9gJ;>I!K(B		 $B7P2a5Z$S=hCV(B
1 $BCK(B
60$BBe(B		 $BK}@-%j%s%Q@-Gr7lIB(B
$B!J$J$7!K(B		 20mg/m2
$B#5F|4V!_#6%/!<%k(B		 $BFCH/@-7l>.HD8:>/@-;gHCIB(B
$BEjM?#3%u7nA0(B $Bpt!$=D3V!$f~c]!$J"It!$$=$1$$%j%s%Q@a$N
$BEjM?3+;OF|(B $BGr7l5e?t(B51900/mm3$B!$0[7?%j%s%Q5e(B91.5$B!s$H$J$j!$#1%/!<%k$r#5F|4V@ECm!\(B23$BF|4V5YLt$H$7$FK\:^EjM?3+;O!#(B
$BEjM?(B156$BF|L\(B
$B!JEjM?=*N;F|!K(B		 $B#6%/!<%kL\EjM?=*N;!#(B
$B=*N;(B27$BF|8e(B $BGr7l5e?t(B5000/mm3$B!$0[7?%j%s%Q5e(B24.0$B!s$H8z2L$,G'$a$i$l$?$,!$7l>.HD?t(B3.2$B!_(B104/mm3$B$HDc24/mm3$B!$5p3K5e?t(B38/mm3$B!$(BPA-IgG$B!J7l>.HD7k9g@-LH1V%0%m%V%j%s(BG$B!K$,(B212ng/107cells$B$H9bCM$G$"$k$3$H$+$i!$FCH/@-7l>.HD8:>/@-;gHCIB!J(BITP$B!K9gJ;$H?GCG!#(B
$B=*N;#4%u7n8e(B $BJ#;k$"$j!$F,It(BMRI$B0[>o$J$7!#93%"%;%A%k%3%j%s%l%;%W%?!<93BN(B79nmol/L$B!J@5>o(B0.2nmol/L$B0J2I6ZL5NO>I!J(BMG$B!K$H?GCG!#(B
$B=*N;#5%u7n8e(B ITP$B5Z$S(BMG$B$KBP$7$F%W%l%I%K%>%m%s(B20mg$B$r3+;O!#(B
$B=*N;#7%u7n8e(B $BJ#;k>C<:!#7l>.HD?t(B5.4$B!_(B104/mm3$B!#(B
$B=*N;#8%u7n8e(B MG$B$NA4?H7?:FG3!#%a%A%k%W%l%I%K%>%m%s!$7l^y8r49$G>I>u7Z8:!#(B
$B=*N;(B12$B%u7n8e(B $B7Z2w!#(B
$B4k6HJs9p(B
$BNW>28!::CM(B
$B!!(B $BEjM?(B73$BF|A0(B $B=*N;(B27$BF|8e(B $B=*N;(B125$BF|8e(B $B=*N;(B374$BF|8e(B
$B@V7l5e?t!J!_(B104/mm3$B!K(B 442 367 417 420
$B7l>.HD?t!J!_(B104/mm3$B!K(B 25.3 3.2 1.7 10.9
$BGr7l5e?t!J(B/mm3$B!K(B 30200 5000 9400 7300
$BJ;MQLt!'$J$7(B



No. $B45 $B#1F|EjM?NL(B
$BEjM?4|4V(B		 $BI{:nMQ(B $BHw9M(B
$B@-(B $B!&(B
$BG/Np(B		 $B;HMQM}M3(B
$B!J9gJ;>I!K(B		 $B7P2a5Z$S=hCV(B
2 $BCK(B
70$BBe(B		 $BK}@-%j%s%Q@-Gr7lIB(B
$B!JE|G"IB!K(B		 12.6mg/m2
$B#5F|4V!_#4%/!<%k(B		 $B@V2j5eat(B
$BEjM?#5G/A0(B $BK}@-%j%s%Q@-Gr7lIB!J(BRai III$B4|!$(BBinet C$B4|!K$H?GCG!#0J8eL$<#NE!#(B
$BEjM?3+;OF|(B $B#1%/!<%k$r#5F|4V@ECm!\Ls(B23$BF|4V5YLt$H$7$FK\:^EjM?3+;O!#(B
$BEjM?(B108$BF|L\(B
$B!JEjM?=*N;F|!K(B		 $B#4%/!<%kL\EjM?=*N;!#(B
$B$=$N8eIO7l$,?J9T!#M"7l$r7+$jJV$7$?$,2sI|$O8+$i$l$:!#(B
$B=*N;(B27$BF|8e(B $B9|?q8!::$r;\9T!#@V2j5e$O(B0.1$B!s$HCx8:$7$F$$$?$?$a!$@V2j5eat$H?GCG!#(B
$B=*N;(B49$BF|8e(B $B%7%/%m%9%]%j%s(B200mg/$BF|$r3+;O$7$?$H$3$m!$M"7l4V3V$O=y!9$K1dD9!#(B
$B=*N;(B80$BF|8e(B $BM"7l$r
$B=*N;(B87$BF|8e(B $B2sI|!#(B
$B=*N;(B122$BF|8e(B $B9|?q8!::$r;\9T!#@V2j5e$O(B12.2%$B$HA}2C$r<($70J9_%X%b%0%m%S%sCM$O(B10$B!A(B12g/dL$BBf$G0\9T$7$F$$$k!#(B
$B4k6HJs9p(B
$BNW>28!::CM(B
$B!!(B $BEjM?#6F|A0(B $B#4%/!<%kEjM?#1F|L\(B $B=*N;(B10$BF|8e(B $B=*N;(B14$BF|8e(B $B=*N;(B42$BF|8e(B
$B@V7l5e?t!J!_(B104/mm3$B!K(B 300 250 187 149 206
$B7l>.HD?t!J!_(B104/mm3$B!K(B 13.1 14.8 11.1 12.1 11.2
$B%X%b%0%m%S%s!J(Bg/dL$B!K(B 9.4 8.5 6.6 5.4 6.8
$BGr7l5e?t!J(B/mm3$B!K(B 90300 34400 25900 25800 24000
$B%j%s%Q5e?t!J!_(B103/mm3$B!K(B 89.4 29.8 22.4 21.8 20.7
$BJ;MQLt!'%0%j%a%T%j%I!$%K%6%A%8%s(B



No. $B45 $B#1F|EjM?NL(B
$BEjM?4|4V(B		 $BI{:nMQ(B $BHw9M(B
$B@-(B $B!&(B
$BG/Np(B		 $B;HMQM}M3(B
$B!J9gJ;>I!K(B		 $B7P2a5Z$S=hCV(B
3 $B=w(B
70$BBe(B		 $BK}@-%j%s%Q@-Gr7lIB(B
$B!J#27?E|G"IB!K(B		 25mg/m2
$B#3F|4V!_#3%/!<%k(B 		$B@V2j5eat(B
$BEjM?(B34$B%u7nA0(B $BK}@-%j%s%Q@-Gr7lIB!J(BB-CLL$B!'(BRai I$B4|!K$H?GCG!#0J8eL5<#NE$G7P2a4Q;!!#(B
$BEjM?3+;OF|(B $B%j%s%Q5eA}2C!$7l>.HD8:>/$,?J9T@-$H$J$j!$%j%s%Q@a2$B!\%7%/%m%[%9%U%!%_%I(B250mg/m2$B!K!_#3F|4V!\(B25$BF|4V5YLt$H$7$FK\:^EjM?3+;O!##3%/!<%k
$BEjM?(B60$BF|L\(B
$B!JEjM?=*N;F|!K(B		 $B#3%/!<%kL\EjM?=*N;!#(B
$B=*N;(B20$BF|8e(B $BIO7l$N?J9T$,L@$i$+$H$J$k!#(B
$B=*N;(B27$BF|8e(B $B%X%b%0%m%S%s(B7.7g/dL$B!$LV>u@V7l5e?t#2"s$HDc2
$B=*N;(B41$BF|8e(B $BIO7l$,?J9T@-$N$?$aF~1!!#?M@V7l5eG;8|1UM"7l!#(B
$B=*N;(B48$BF|8e(B $B%7%/%m%9%]%j%s!J(B250mg$B!KEjM?3+;O!#(B
$B=*N;(B153$BF|8e(B $B2sI|!#(B
$B4k6HJs9p(B
$BNW>28!::CM(B
$B!!(B $BEjM?#6F|A0(B $B=*N;#6F|8e(B $B=*N;(B40$BF|8e(B $B=*N;(B153$BF|8e(B
$B@V7l5e?t!J!_(B104/mm3$B!K(B 457 409 224 430
$B%X%b%0%m%S%s!J(Bg/dL$B!K(B 14.1 12.8 6.5 13
$B7l>.HD?t!J!_(B104/mm3$B!K(B 11.4 9.6 28.2 19.9
$BGr7l5e?t!J(B/mm3$B!K(B 129400 3500 9800 10600
$BJ;MQLt!'%7%/%m%[%9%U%!%_%I!$C:;@?eAG%J%H%j%&%`!$%"%m%W%j%N!<%k!$;@2=%^%0%M%7%&%`!$%0%j%/%i%8%I!$%F%W%l%N%s(B



2.$B;HMQ>e$NCm0U$N2~D{$K$D$$$F!J$=$N#1#7#0!K(B
$B!!A0!99f!J0eLtIJ!&0eNE5!4oEy0BA4@->pJs(B No.217$B!K0J9_$K2~D{$r;XF3$7$?0eLtIJ$N;HMQ>e$NCm0U!JK\9f$N!V#1!!=EMW$JI{:nMQEy$K4X$9$k>pJs!W$G>R2p$7$?$b$N$r=|$/!#!K$K$D$$$F!$2~D{FbMF!$!$;29MJ88%Ey$r$*CN$i$;$$$?$7$^$9!#(B

1 $B!RIT@0L.MQ:^!S(B
$B1v;@%Y%W%j%8%k(B

$B!NHNGdL>!O(B $B%Y%W%j%3!<%k>{(B50$B!$F1>{(B100$B!JF|K\%*%k%,%N%s!K(B
$B!NI{:nMQ(B
$B!J=EBg$JI{:nMQ!K!O(B		 QT$B1dD9!$(B$B?4<$B!$?4<<:YF0(B$B!'(BQT$B1dD9!$(B$B?4<$B!$?4<<:YF0!$%"%@%`%9!&%9%H!<%/%9>I8u72(B$B$,$"$i$o$l$k$3$H$,$"$k$N$G!$Dj4|E*(B$B$+$DI,MW$K1~$8$F(B$B?4EE?^8!::$r9T$$!$0[>o$JJQF0(B$B$d>I>u$,G'$a$i$l$?(B$B>l9g$K$OEjM?$rCf;_$7!$(B$B%j%I%+%$%s!$N2;@%^%0%M%7%&%`$N@ECm!$=|:YF0$d%Z!<%7%s%0Ey$N(B$BE,@Z$J=hCV$r9T$&$3$H!#(B
$B!R;2!!!!!!9M!S(B $B4k6HJs9p(B

2 $B!RBe $B%7%?%i%S%s(B$B!JBgNLNEK!MQ@=:^!K(B

$B!NHNGdL>!O(B $B%-%m%5%$%I(BN$BCm!JF|K\?7Lt!K(B
$B!N7Y9p!O(B
$B7Y9p(B
$B%7%?%i%S%sBgNLNEK!!J0J2$B$^$?!$6[5^0eNEBN@)$N@0Hw$5$l$?0eNE5!4X$K$*$$$F(B$B$,$s2=3XNEK!(B$B$K==J,$JCN<1$H7P83$r;}$D0e;U$N$b$H$G(B$BK\NEK!$,E,@Z$HH=CG$5$l$k>INc$K$D$$$F$N$_$B$3$H!#(B$BB>$N93l9g!$E,1~45H$7$F==J,Cm0U$9$k$3$H!#(B
$B!NMQK!!&MQNL$K4XO"(B
$B$9$k;HMQ>e$NCm0U!O(B		 $B5^@-%j%s%Q@-Gr7lIB5Z$S0-@-%j%s%Q$N93H$9$k$3$H!#(B
$B!R;2!!!!!!9M!S(B $B4k6HJs9p(B

3 $B!RI{?U%[%k%b%s:^!S(B
$B%G%-%5%a%?%>%s(B$B!J7P8}:^!K!J930-@-C2=4o>I>u$N8zG=$rM-$7$J$$@=:^!K(B
$B?];@%G%-%5%a%?%>%s(B
$B%j%s;@%G%-%5%a%?%>%s%J%H%j%&%`(B$B!JCm
$B!NHNGdL>!O(B $B%G%+%I%m%s%(%j%-%7%k!Jh_M-@=Lt!K!$%G%-%5!&%^%^%l%C%H!J>%s>{!J002=@.!K!J002=@.%U%!!<%^!K!$%G%-%5%a%5%>%s(BE$B!JElOBLtIJ!K!$%G%-%5%a%5%>%s%(%j%-%7%k!V%K%C%7%s!W!JF|?7@=Lt!K!$%_%?%>!<%s!JElMN%U%!%k%^!$B?];@%G%-%5%a%?%>%s7|ByCm!JIY;N@=Lt9)6H!K(B
$B%=%k%3!<%HCm!JIY;N@=Lt9)6H!K!$%G%m%s(BS$BCm!JElOBLtIJ!K(B
$B!N86B'6X4w!O(B
$B%3%s%H%m!<%kITNI$NE|G"IB$N45
$B!NI{:nMQ(B
$B!J=EBg$JI{:nMQ!K!O(B		 $B>C2=@-DYag(B$B!$>C2=4I@|9&(B$B!$g91j(B
$B9|AFr">I!$BgB\9|5Z$S>eOS9|Ey$N9|F,L56]@-2u;`!$%_%*%Q%7!<(B$B!$@TDG05Gw9|@^!$D99|$NIBE*9|@^(B
$B7l@r(B$B:I@r(B$B>I(B
$B!R;2!!!!!!9M!S(B $B4k6HJs9p(B

4 $B!RI{?U%[%k%b%s:^!S(B
$B%Q%k%_%A%s;@%G%-%5%a%?%>%s(B
$B!NHNGdL>!O(B $B%j%a%?%>%s!J;0I)%&%'%k%U%!!<%^!K(B
$B!N86B'6X4w!O(B
$B%3%s%H%m!<%kITNI$NE|G"IB$N45
$B!R;2!!!!!!9M!S(B $B4k6HJs9p(B

5 $B!RI{?U%[%k%b%s:^!S(B
$B%W%i%9%F%m%sN2;@%J%H%j%&%`(B$B!JCm
$B!NHNGdL>!O(B $B%^%$%j%9Cm!JF|K\%*%k%,%N%s!KB>(B
$B!N7Y9p!O(B
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$B#2!K(B U. S. FDA$B!'(BGuidance for Industry Pharmacogenomic Data Submissions$B!J(B2005$B!K(B
$B#3!K(B Werner Kalow$B!$(Bet al.$B!'%U%!!<%^%3%2%N%_%/%9!](B21$B@$5*$NAOLt$H8D$N0eNE!]!J@P@nCR5W4FLu!K!$%F%/%N%_%C%/!J(B2002$B!K(B
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$B#5!K(B Pharmacogenomics$B!'93$,$s:^FC=8!J(BNature Asia-Pacific$B!$(B2005$B!K(B
$B#6!K(B Aithal GP, Day CP, Kesteven PJ, Daly AK$B!'(BAssociation of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet$B!$(B353$B!'(B717-719$B!J(B1999$B!K(B
$B#7!K(B Meyer UA$B!%(BDrugs in special patient groups$B!'(Bclinical importance of genomics in drug effects In$B!'(BGS Carruthers$B!$(BBB Hoffman, KL Melmon, DF Nierenberg, eds. Melmon and Morelli's Clinical Pharmacology. New York$B!'(BMcGraw-Hill$B!$(Bpp.1179-1205$B!J(B2000$B!K(B
$B#8!K(B Furuta T$B!$(BOhashi K$B!$(BKobayashi K$B!$(BIida I$B!$(BYoshida H$B!$(BShirai N$B!$(BTakashima M$B!$(BKosuge K$B!$(BHanai H$B!$(BChiba K$B!$(BIshizaki T$B!$(BKaneko E$B!'(BEffects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans. Clin Pharmacol Ther$B!$(B66$B!'(B265-274$B!J(B1999$B!K(B
$B#9!K(B Monaghan G$B!$(BRyan M$B!$(BSeddon R$B!$(BHume R$B!$(BBurchell B$B!'(BGenetic variation in bilirubin UDP-glucuronosyltransferase gene promoter and Gilbert's syndrome. Lancet$B!$(B347$B!'(B578-581$B!J(B1996$B!K(B
10$B!K(B Ando Y$B!$(BChida M$B!$(BNakayama K$B!$(BSaka H$B!$(BKamataki T$B!'(BThe UGT1A1*28 allele is relatively rare in a Japanese population. Pharmacogenetics$B!$(B8$B!'(B357-360$B!J(B1998$B!K(B
11$B!K(B Ando Y$B!$(BSaka H$B!$(BAndo M$B!$(BSawa T$B!$(BMuro K$B!$(BUeoka H$B!$(BYokoyama A$B!$(BSaitoh S$B!$(BShimokata K$B!$(BHasegawa Y$B!'(BPolymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity$B!'(BA pharmacogenetic analysis$B!%(BCancer Res$B!$(B60$B!'(B6921-6926$B!J(B2000$B!K(B
12$B!K(B Iyer L$B!$(BRatain MJ$B!'(BPharmacogenetics and cancer chemotherapy$B!%(BEur J Cancer$B!$(B34$B!'(B1493-1499$B!J(B1998$B!K(B
13$B!K(B Drews J$B!$(BRyser S$B!'(BThe role of innovation in drug development$B!%(BNat Biotechnol$B!$(B15$B!'(B1318-1319$B!J(B1997$B!K(B
14$B!K(B Navis G$B!$(BFG van der Kleij$B!$(BD de Zeeuw$B!$(BPE de Jong$B!'(BAngiotensin-converting enzyme gene I/D polymorphism and renal disease$B!%(BJ Mol Med$B!$(B77$B!'(B781-791$B!J(B1999$B!K(B



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