ESL ()-methyl 3-{4-[2-hydroxy-3-(isopropylamino)pro poxy]phenyl} propanoate monohydrochloride H 3 C O O JAN( ) JAN( )esmolol hydrochloride r-inn( )esm
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- みちしげ にかどり
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1 (1) (2) (ISAintrinsic sympathomimetic activity) 199 (3) ( MSAmembrane stabilizing activity) 2 (4) 21 (5) 212 (6) 216 (7) 219 (8) 224 (9) (ASL-8123) (1) d-esl l-esl (1) ESL 237 (2) (ASL-8123) 24 (3) d-esl l-esl 243
2 ESL ()-methyl 3-{4-[2-hydroxy-3-(isopropylamino)pro poxy]phenyl} propanoate monohydrochloride H 3 C O O JAN( ) JAN( )esmolol hydrochloride r-inn( )esmolol O H OH H N CH 3 CH 3 HCl d-esl ()-methyl 3-{4-[2-hydroxy-3-(isopropylamino)pro poxy]phenyl} propanoate monohydrochloride H 3 C O O O OH H N CH 3 CH 3 HCl ESL d l-esl ()-methyl 3-{4-[2-hydroxy-3-(isopropylamino)pro poxy]phenyl} propanoate monohydrochloride H 3 C O O O OH H N CH 3 CH 3 HCl ESL l ASL {4-[2-hydroxy-3-(isopropylamino) propoxy]phenyl}propanoic acid monohydrochloride HO O O OH H N CH 3 CH 3 HCl
3 ( ) APA AP5 AP1 EC5 EC8 EC95 HPLC i.v. IC5 ISA Kd Ki LD5 LOQ LV dp/dt MAC MSA NE NLA Post EC5 Pre EC5 QTc RMP RPP SNP TOF TTC Vmax WB % 8% 95% 5 (intrinsic sympathomimetic activity) 5 (minimal alveolar concentration) (membrane stabilized action) (Neurolept analgesia) 5% 5% QT (QT / ) (Rate Pressure Product) 2-([2,6- ]-1,4-
4 31-7 M pa2 ( 1)6.82 (in vitro- ) 31-5 M( ) 11-5 M ( 2)5.18 ( 2) M( 1/ 2 / ) / (in vitro- ) M 11-2 M 313 (in vivo) g/kg/ (i.v. ) 131 g/kg/ (i.v. ) 11-8 M 11-3 M 11-6 M 11-8 M 11-3 M 31-9 M (ISA) 11-3 M Ki (nm) / pa (5 ).19 g/ml 1) 5 1 g/kg/ g/kg/ g/kg/ M 11-4 M 11-7 M 31-8 M1 1-5 M(31-6 M 12.4) 5 ( 11 ( )5 6 MSA) 5 L( ).313 mg/kg 7 (i.v. ) PR 3mg/kg.3 3mg/kg ESL ( 1 ) g/ml(.3mg/kg) g/ml(1mg/kg) g/ml(3 mg/kg) 15 ISA (intrinsic sympathomimetic activity) MSA (membrane stabilizing activity) 1) 186
5 mg/kg (i.v. ) 1 mg/kg (i.v. ) NLA 1 mg/kg (i.v. ) g/kg/ (i.v. ) 31 g/kg (i.v. ) 11 g/kg (i.v. ).111 g/kg/ (i.v. ).313 mg/kg (i.v. 18 ) 8.3mg/kg 1mg/kg PR QTc 3mg/kg ( 1 ) g/ml(.3mg/kg) g/ml (1mg/kg) g/ml(3mg/kg) 3 PR ( 1 ) g/ml PR QT ( 1 ) g/ml 15 (5)35.6 g/kg/ (5)249 g/kg g/kg 1 1 g/kg/ 1 mg/kg mg/kg12.4 ( 42.1) mg/kg (i.v. ) 187
6 18 d 31-6 M 31-6 M 31-6 M 31-5 M 31-6 M 254 g/kg/ (i.v. ) ESL MAC ESL EC EC95 1 d EC d ESL SNP (ASL 8123) l ESL 31 - M (in vitro) 11-2 M (in vivo) mg/kg/ (i.v. ) pa (5 )293 g/ml 31-7 M (in vitro) 31-5 M ( ) (in vitro- ) 11-5 M 11-4 M ( ) M 11-2 M pa2 ( )desl6.7lesl 7.36ESL7.12 pa2 ( )lesl5.53esl5.41 desl Ki (nm) lesl Ki (nm) / 2 desl=1.74lesl=
7 ESL in vitro in vivo 2 ESL 3 ESL ESL ESL ESL ASL8123 ESL desllesl pa2 1/ 2 ESL 1 1 (ESL )ESL Ki ESL Ki 2/Ki 1 1 (ESL )ESL 1 In vivo ESL pa ESL ESL 6 ESL 11-6 M 11-7 M ESL 11-4 M ESL (11-7 M11-6 M) 189
8 ESL ISA M ESL MSA 5.2 MSA ESL.31 3mg/kg.3mg/kg 3mg/kg PR ESL.3mg/kg 1mg/kg 3mg/kg PR QTc ESL 1mg/kg PR NLA ESL 1mg/kg PR QT ESL 3mg/kg 1 3mg/kg 3 NLA 1mg/kg 1 3 ESL ESL g/kg/ 249 g/kg 1 1 g/kg 1 1 g/kg/ ESL 1 3mg/kg ( ) ( ) ESL rate pressure product ESL 19
9 ESL ESL.5 1 MAC ESL (4) ( NLA) ESL EC95 1 d EC95 3 ESL ESL ESL ESL SNP ASL8123 pa (ESL 6.82) ASL g/ml(esl.19.4 g/ml) ASL8123 ESL In vitro desl lesl pa desl lesl 1 (Ki ) nm desl lesl in vivo 1mg/kg desl 72 / lesl 87 / 191
10 ESL ( ) ( 1 WB411( 1 ) ( 2 ) in vitro in vivo (Hartley 1 6 ) ESL M M M M M M M M M ( 1) ( 2) pa2 ( EC5 ) 1 ( 1/ 2) ESL - pa2 ( 1) ( 2) ( 2) ( 1/ 2) / / ESL ESL pa2 ESL 1-1 ( 1) ( 2) ( 2) 1 ( 1/ 2) pa2 pa2 pa2 / / slope slope slope (95 ) (95 ) (95 ) ESL (.7.95) ( ) (.3.84) (.61.86) (.681.8) (.27.88) (.61.15) ( ) ( ) antilog( pa2 pa2 )
11 (Wistar ) ( 1- )( 2- ) ( 1-2- ) 23 ( ) ESL 11-2 M M 11-2 M( 1-2- ) M( 1-2- ) M M 11-3 M( 1-2- ) 11-6 M( 1-2- ) M M - WB M M (Ki ) Ki 1/Ki 2 ESL Ki (nm) 1-2- Ki 1- (Ki 1/ Ki 2) ESL ESL ESL 1- ( 3) - Ki ESL Ki 2/Ki ESL Ki (nm) Ki 2/ Ki ESL 45 (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) WB Ki 2/ Ki 1 Ki IC5/(1+[L]/Kd)[L] (M)Kd IC5 5 (M) WB4112-([2,6-Dimethoxyphenoxyethyl]-1,4-benzodioxane Hydrochloride
12 (1 5 ) ESL 31 3 g/kg/ g/kg 2 pa2 ( ED5 ) ESL ESL ( 1) pa ESL 4 µ 2 µ µ pa ( 4) ESL ESL in vivo µ µ 2 µ µ µ ESL µ µ µ µ µ µ µ µ
13 pa2( ) Slope( ) 95% ESL (1 56 ).5 g/kg ESL 13 1 g/kg/ 2.4 g/kg/ 18 1 () 1 5 ESL 13 1 g/kg/ g/kg/ ( 2) ESL µ µ µ µ
14 ESL ( ) ESL M 345 ESL (NE.2.4g/mL.1.2g/mL) ESL M 615% 11-3 M g/ml NE ESL 11-7 M 11-6 M 78%.4g/mL NE ESL 11-7 M ( 3) ESL M ( 5).1.2 g/ml NE 658 ESL 11-7 M 325 NE 11-6 M ESL ( 4) ESL 11-3 M M 615% ESL ISA ESL 11-4 M NE 3 25 ESL ISA ESL 11-4 M M 1 ESL ( ) - 196
15 NE NE ESL () ESL () NE NE 197
16 ( ) 3M 1 ESL M 153 (RMP) (APA) (Vmax) 5 1 (AP5 AP1) ESL.2.5g/mL ESL M 153 ESL M (RMP) 11-3 M RMP ESL 11-4 M (APA) (Vmax) 5 1 (AP5AP1) ( 6 5).2.5 g/ml ESL 11-7 M 13 - ESL.2.5 g/ml 11-7 M 1-4 M ESL 1mg/kg 1. g/ml ( ) M 1/3 ESL M ESL RMP ESL ISA ESL (M) RMP APA Vmax AP1 AP p <.5 p <.5 RPM APA Vmax AP11% AP55% 198
17 (Hartley 1 47 ) ESL M ISA - ISA M M M M 1 ESL M (11-6 M 12.4) 11-5 M 31-5 M ( 7) ESL ISA ISA - ISA 199
18 p.5 p.1(unpaired t ) (Hartley 1 56 ) (5 L) (5 L) ESL ( ) ESL 5 MSA.2 1. MSA ( 6) ESL MSA ESL (1mg/kg 1. g/ml )5, ESL 2
19 () () ESL /5 /5 /5 1 /5 /5 /5 /6 /6 /6 2.5 /6 /6 /6 /6 /6 /6 /5 5 6/6 5/6 /6 /5 /6 /6 /6 /6 1 6/6 6/6 3/6 /6 /6 /6 /6.1 3/6 /6 /6 /6 /6 /6 /6.2 6/6 6/6 5/6 /6 /6 /6 /6 1 4/6 /6 /6 /6 /6 /6 /6 2 6/6 6/6 3/6 /6 / p.5(fisher ) (1 4 ) ESL.31 3mg/kg (PR QRS QT QTc) ( ) ESL HPLC ESL ESL ( 8 9) ESL 3mg/kg PR ( 1)ESL.33mg/kg ESL 1.3mg/kg g/ml 1mg/kg g/ml3mg/kg g/ml 15 (.11 g/ml 11) ESL 3mg/kg 3mg/kg PR.33mg/kg 21
20 (n=4) (n=4) ESL 3 22
21 (n=4) ESL 3 p.5 p.1(dunnett ) ESL.3mg/kg ESL 1mg/kg ESL 3mg/kg LOQ(.11µg/mL) ESL LOQ 23
22 1 4 (1.52.5) ( 73) 6mg/kg 24mg/kg/ ( 73) NLA (.75mg/mL) (.15mg/mL) (1mL/kg).5 1.5mg/kg/.1.3mg/kg/ ( 73) ESL (.31 3mg/kg NLA 1mg/kg) ( ) (PR QRS QT QTc) ESL 21 ESL 12 ESL ( ) 15 ( 14) (931) (1537) (252) ( 13)ESL 1 3mg/kg (3 23) (37 38) 5 ( 14)3mg/kg 1 PR (12) 5 QTc ( 1) ( 15) ESL 1.3mg/kg g/ml1mg/kg g/ml3mg/kg g/ml 3 ( 24) 16 ESL 1mg/kg 15 ( 16) 15 ( 4)( 17) 3 ( 18) 3 ( 24)( 18) PR 1 ( 13) ( 19) ESL g/ml 15 ( 24) NLA 2 NLA NLA ESL 1mg/kg 15 ( 17) ( 17) ( 21) ( 26)( 22) PR ( 16) QT ( 16) ( 23) ESL
23 g/ml 15 ( 24) NLA ESL.3 3mg/kg1mg/kg1mg/kg ESL - ) ESL 31 g/kg/ PR QRS 3 HV AH SH class 1 HV ESL ESL mg/kg 1.mg/kg ) (21 ) 3mg/kg ) ESL 31 g/kg/ LV dp/dtmaxrate pressure products ESL ESL - 25
24 (n=4) (n=4) ESL 3 p.5 p.1(dunnett )
25 (n=4) ESL 3 p.5 p.1(dunnett ) (n=4) ESL 3 p.5 p.1(dunnett ) 27
26 (n=4) (n=4) ESL 3 p.5(student t )
27 (n=4) ESL 3 p.5 p.1 (Student t ) (n=4) ESL 3 p.5(student t ) 29
28 (n=4) (n=4) ESL 3 p.5 p.1 (Student t ) 21
29 (n=4) ESL 3 p.5 p.1 (Student t ) (n=4) ESL 3 p.5 p.1 (Student t ) 211
30 1 1 ESL.3mg/kg ESL 1mg/kg ESL 3mg/kg 1 1 ESL 1mg/kg 1 1 ESL 1mg/kg.1 LOQ(.11µg/mL).1 LOQ(.11µg/mL).1 LOQ(.11µg/mL) ESL LOQ: ESL (1 35 ).5 g/kg ESL g/kg/ g/kg/ 6 () 1 5 ESL ( 25)ESL g/kg/ g/kg/ ESL 1/13 212
31 (1 6 ) 5 ESL g/kg g/kg( g/kg) ESL 1 5 () 1 () 5 ESL (19 )5 ESL ESL ESL 3 g/kg g/kg g/kg g/kg ( ) 1 g/kg g/kg g/kg g/kg ( 26)ESL g/kg 5 48 g/kg ESL 1/5 213
32 µ (1) 5 ) (1.55.5g/kg/) 3 ESL 1 1 g/kg 3 3 g/kg 3 3 g/kg ESL.1 1 g/kg/ 2 (2 ) ESL 1 g/kg 1 g/kg/ ( 27) 3 g/kg ( 28) ESL 214
33 µ µ µ µ µ (n=5) p.5 p.1(dunnett ) µ µ µ µ (n=5) p.5 p.1(dunnett ) 215
34 ESL (1 6 ) 2 cm 3 3 ESL.33mg/kg 2 3mg/kg ,3,5 (TTC) 1cm ( ) ( TTC ) ABC 3 D ESL 6 rate pressure product(rpp) ( 29) ( 7)ESL 1mg/kg 3mg/kg 3mg/kg ( ) ( ) ( 3) ESL 1 3 mg/kg ESL RPP ) (1 5 ) ESL.5mg/kg/ 2 4 () ESL
35 (A) (B) (C) RPP(rate pressure product) (n6) p.5 p.1(dunnett ) 217
36 (mg/kg) (ml//g) ESL (5) 6 6(5) (5) ESL.3 3.mg/kg 1 1cm 3 ABC D (ABC)/3 ()( / )1 (n6) p.5 p.1(dunnett ) 218
37 (1 45 ) ESL.3 1mg/kg ( ) g/kg/ 1 ESL.1.3 1mg/kg 1 (ESL )ESL mg/kg 3 / /3 ESL.3mg/kg 12 1 ESL1mg/kg mg/kg 33 ( 31) ESL.3 1mg/kg 15.3 mg/kg 11 3 ( 31) ( 32A) ( 32C) / ( 32D) ( 32E).1 g/kg/ ( 31) ( 32A) ( 32B) ( 32C) / ( 32D) ( 32E) ESL.11mg/kg / ESL.1 1mg/kg.3 mg/kg / 219
38 ESL ESL1mg/kg 2 / ESL ESL ESL ESL.11mg/kg 22
39 (A) (B) (C) µ µ (A)n=4(BC)n=5 p.5 p.1(dunnett test) 221
40 (A) (B) ().1 g/kg/ p.5(dunnett test) 222
41 (C) (D) (E) ().1 g/kg/ p.5 p.1(dunnett test) 223
42 (Hartley ) 5 (Pre EC5) ESL 31-6 M ( ).5 1. MAC ESL 31-6 M 1 5 (Post EC5) ESL ESL Post/Pre Post/Pre ESL Post/Pre MAC Post/Pre ( 8) ESL 1 MAC Pre EC5 (M) Post EC5 (M) Post/Pre ( ) Pre EC5(M)ESL 5 Post EC5(M)ESL 5 (Hartley 1 8 ) 5 (Pre EC5) ESL 31-6 M ESL M ( d )EC (Post EC5) ESL ESL Post/Pre Post/Pre
43 ESL Post/Pre EC d Post/Pre ( 9) d EC95 1 Post/Pre Post/Pre ( 1) EC95 1 ( 11) ESL EC95 1 d EC95 1 ESL (M) Pre EC5 (M) Post EC5 (M) Post/Pre ( ) d Pre EC5(M)ESL 5 Post EC5(M)ESL 5 (M) Pre EC5 (M) Post EC5 (M) Post/Pre ( ) d p.5(dunnett ) Pre EC5(M)ESL 5 Post EC5(M)ESL 5 (M) Pre EC5 (M) Post EC5 (M) Post/Pre ( ) Pre EC5(M)ESL 5 Post EC5(M)ESL 5 225
44 (Hartley 1 3 ) 2.2 2Hz 4 (TOF ) EC8 ( M) d ( M) ESL 31-6 M 31-5 M ESL TOF 1 (T1) 1 T1 d ( EC8 ) ESL 31-6 M 31-5 M ( 12) ESL ESL 1) 2) ESL (M) ESL 31-6 M ESL 31-5 M d p.1(dunnett ) T1 1 T1 1) Murthy V.S., et. al. : Effects of esmolol on circulatory response to intubation and succinylcholine-induced neuromuscular blockade in man. Anesthesiology, 63, 3A, ) Szmuk P., et. al. : The onset time of rocuronium is slowed by esmolol and accelerated by ephedrine. Anesth. Analg., 9, , 2 226
45 (Hartley 1 8 ) 5 (Pre EC5) ESL 31-6 M ( ) ESL 31-6 M 1 5 (Post EC5) ESL ESL Post/Pre Post/Pre M ESL 31-6 M Post/Pre M ESL 31-6 M Post/Pre ESL ( 13) ESL Ca 1) (M) Pre EC5 (M) Post EC5 (M) Post/Pre ( ) p.5(dunnett ) Pre EC5(M)ESL 5 Post EC5(M)ESL 5 1) 2.4 (199) 227
46 (1 1 ).3 (SNP) 6mmHg ESL 6mmHg 254 g/kg/ 6 6mmHg SNP SNP ESL 6mmHg SNP SNP g/kg/ ESL251 4 g/kg/ SNP g g/kg/( ) ESL SNP SNP 3 ( 33)ESL SNP ESL ESL SNP µ µ µ µ ESL ( g/kg/) SNP 9.6 ( g/kg/) (n1) ( ) p.5 p.1(dunnett ) 228
47 ESL ASL8123 in vitro in vivo ESL (148) ASL M 1 ( 1) ( 1) pa2( EC5 ) ASL M 11-2 M 257 / ASL8123 ( 34) pa ASL M ASL8123 ( 1) pa ESL pa (192 )ASL8123 ESL 1/1 (Shaffer J.E. et al.: -adrenoreceptor antagonist potency and pharmacodynamics of ASL-8123, the primary acid metabolite of esmolol. J. Cardiovasc. Pharm. 11, , 1988) 229
48 (1 6 ).5 g/kg 1 ASL mg/kg/ 2 ( mg/kg) ASL ASL8123 ASL mg/kg / ASL mg/kg ASL mg/kg ASL mg/kg 5 ASL g/ml( 35)(ESL.19.4 g/ml )) ASL8123 ESL 1/1 5 ASL8123 (Shaffer J.E. et al.: -adrenoreceptor antagonist potency and pharmacodynamics of ASL-8123, the primary acid metabolite of esmolol. J. Cardiovasc. Pharm. 11, , 1988) 23
49 ESL desllesl d lesl (Hartley 1 56 ) desl lesl ESL M 1 ( 1) 3 desllesl ESL M 1 ( 2) ( 1) ( 2) pa2 ( EC5 ) desllesl ESL ( 36) pa ( 14)lESL ESL ( 37) pa ( 14) desl 11-4 M pa2 desl lesl ESL 1 desl 2 lesl ESL 2 desl lesl in vivo 1mg/kg desl 72 / lesl 87 / (243 ) ESL d-esl l-esl pa2( ) Slope( ) 95% ) 1) 1) ) 1-4 M 231
50 M 1-9 M 1-1 M 1-9 M M 1-7 M 1-6 M 1-5 M M 1-7 M 1-6 M 1-5 M M 1-9 M 1-1 M 1-9 M 1-8 M 1-7 M 1-6 M 1-5 M 1-8 M 1-7 M 1-6 M 1-5 M M 1-9 M 1-1 M 1-9 M 1-8 M 1-7 M 1-6 M 1-5 M 1-8 M 1-7 M 1-6 M 1-5 M 1-1 M 1-9 M 1-8 M 1-7 M 1-6 M 1-5 M 1-1 M 1-9 M 1-8 M 1-7 M 1-6 M 1-5 M 1-1 M 1-9 M 1-8 M 1-7 M 1-6 M 1-5 M 232
51 M 1-9 M 1-8 M 1-7 M 1-6 M 1-5 M 1-4 M 1-8 M 1-7 M 1-6 M 1-5 M 1-4 M M 1-9 M 1-8 M 1-7 M 1-6 M 1-5 M 1-4 M 1-8 M 1-7 M 1-6 M 1-5 M 1-4 M M 1-9 M 1-8 M 1-7 M 1-8 M 1-7 M 1-6 M 1-5 M 1-4 M 1-6 M 1-5 M 1-4 M 1-9 M 1-8 M 1-7 M 1-6 M 1-5 M 1-4 M 1-9 M 1-8 M 1-7 M 1-6 M 1-5 M 1-4 M 1-9 M 1-8 M 1-7 M 1-6 M 1-5 M 1-4 M 233
52 (Wistar ) ( 1 ) ( 2 ) ( 1 2 ) ESLdESL lesl 23 ( ) ESLdESL lesl 11-2 M M WB M M (Ki ) Ki desl lesl (nm) desl lesl Ki 1 2 Ki desl lesl 1/ Ki desl lesl (nm) ( 15) 1 2 leslesldesl 1/ 2 ESLlESLdESL 1 2 ESL desl lesl Ki(nM) Ki 2/ Ki (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) (1 3 ) WB Ki 2/ Ki 1 Ki IC5/(1+[L]/Kd)[L] (M)Kd IC5 5 (M) WB4112-([2,6-Dimethoxyphenoxyethyl]-1,4-benzodioxane Hydrochloride
53 ESL ASL8123 desllesl ESL 1mg/kg ESL 11-5 g/ml(31-5 M) 11-4 g/ml(31-4 M) 11-3 g/ml(31-3 M) 11-4 g/ml(31-4 M) 11-4 g/ml(31-4 M) ESL 11mg/kg 3mg/kg 3mg/kg 1 mg/kg 11-4 g/ml ESL 1mg/mL ASL8123 1mg/kg 6 ASL8123 1mg/kg ASL ASL g/ml 11-4 g/ml 11-5 g/ml ASL8123 1mg/kg ASL8123 3mg/mL ASL g/ml ESL desllesl 2.52mg/kg 6 desl lesl 11-4 g/ml 11-4 g/ml desl 52mg/kg lesl 2.51mg/kg desl 1mg/kg 15 2mg/kg 1 desl lesl desl lesl 11-4 g/ml 235
54 ESL desl lesl ASL g/ml ESL M31-6 M( g/ml192 ) ESL 11 ESLdESL lesl (192 ) leslesld-esl ( 22) l d-esl ESL ASL8123 1mg/kg 11-3 g/ml ASL8123 ESL ESL ESLASL8123dESL lesl 236
55 16 ESL 11-4 g/ml(31-4 M) 11-3 g/ml(31-3 M) 11-5 g/ml(31-5 M) g/ml(31-4 M) 11-3 g/ml(3 1-3 M) 11-4 g/ml(3 1-4 M) 11-4 g/ml(31-4 M) 11-4 g/ml(31-4 M) ESL 13 1mg/kg 3mg/kg PR 3 mg/kg QT QRS QTc mg/kg 45 3 mg/kg 1 mg/kg ) ESL 1.258mg/kg mg/kg ESL 1mg/mL 237
56 (1 ) (Irwin (6) ) (15) ( (6) ) ( ) (6) ( Writhing ) (6) mg/kg 131 mg/kg 131 mg/kg 131 mg/kg 131 mg/kg 131 (6) mg/kg ( ) 131 (1) mg/kg in vitro 11-6 (4) 11-4 g/ml ( M) in vitro 11-5 (6) 11-3 g/ml ( M) in vitro 11-6 (4) 11-4 g/ml ( M) in vitro 11-6 (4) 11-4 g/ml ( M) in vitro 11-6 (6) 11-3 g/ml ( M) 11-5 g/ml(31-5 M) g/ml(3 1-4 M) 11-3 g/ml(31-3 M) 11-4 g/ml(31-4 M) 11-4 g/ml(31-4 M) 11-4 g/ml(31-4 M)
57 239 (1 ) ( ) (3) 131 mg/kg (3) 131 mg/kg 3mg/kg ( ) (3) 131 mg/kg 3mg/kg PR QT QRS QTc (3) 131 mg/kg 11mg/kg 45 (3) 131 mg/kg 3mg/kg (3) 131 mg/kg 1mg/kg (6) 131 mg/kg (67) 131 mg/kg (56) 131 mg/kg (6) 131 mg/kg (46) 131 mg/kg (56) 131 mg/kg (67) 131 mg/kg (6) in vitro 131 mg/ml 1mg/mL
58 ASL8123 1mg/kg ASL8123 1mg/kg ASL g/ml 11-3 g/ml 11-3 g/ml 11-4 g/ml 11-3 g/ml g/ml 11-5 g/ml 11-3 g/ml ASL8123 1mg/kg g/ml 11-3 g/ml 3mg/mL 24
59 (1 ) 131 (Irwin (6) ) 13 1mg/kg 1 3mg/kg 1 mg/kg mg/kg (6) 31 mg/kg ( (6) ) ( ) (6) ( Writhing ) (6) (6) (6) ( ) 13 1mg/kg 13 1mg/kg 13 1mg/kg 13 1mg/kg in vitro 11-5 (6) 11-3 g/ml in vitro 11-5 (6) 11-3 g/ml in vitro 11-5 (6) 11-3 g/ml in vitro 11-6 (6) 11-3 g/ml in vitro 11-5 (6) 11-3 g/ml ( ) 11-3 g/ml 11-3 g/ml 11-3 g/ml g/ml 11-3 g/ml g/ml g/ml g/ml 241
60 (1 ) (6) mg/kg (6) mg/kg (6) mg/kg (6) mg/kg in vitro 11-5 (6) 11-3 g/ml (6) mg/kg (6) mg/kg in vitro (6) 131 mg/ml 1 mg/kg 1 mg/kg g/ml 11-3 g/ml 3 mg/ml 242
61 18 desl 52mg/kg 12mg/kg 5 2mg/kg 2mg/kg lesl 2.51mg/kg 2.5 1mg/kg 1mg/kg desl lesl 5 1 desl lesl 1 desl lesl g/ml g/ml g/ml g/ml desl lesl g/ml 11-3 g/ml desl 1mg/kg 15 2mg/kg 1 desl lesl desl 52mg/kg (1mg/kg 1 72 / ) lesl 2.51mg/kg (1mg/kg 1 87 / ) lesl desl desl lesl 1mg/mL 243
62 (1 ) (4) (Irwin ) g/ml lesl (desl) 512 (lesl) mg/kg (6) in vitro 11-6 (4) 11-4 g/ml ( 1) in vitro 11-6 (4) 11-4 g/ml in vitro 11-6 (4) 11-4 g/ml ( 1) in vitro 11-6 (6) 11-3 g/ml ( 3) (desl) (6) 512 (lesl) mg/kg in vitro (6) desl 52mg/kg 12mg/kg 5 2mg/kg 2mg/kg lesl 2.51mg/kg 2.5 1mg/kg 1mg/kg desl lesl mg/ml desl lesl 11-4 g/ml desl lesl g/ml g/ml desl lesl desl lesl 11-4 g/ml g/ml desl 1mg/kg 15 2mg/kg 1 desl desl 1mg/kg 72 /( 1 ) lesl 1mg/kg 87 /( 1 ) 1mg/mL 244
(1) (2) (1) (2) (1) Seg (2) Seg (3) Seg (4) Seg (1) (2) (3) ( ) (1) (PCA)...12
(1)...109 (2)...110 (1) 28...111 (2) 28...113 (1) Seg...115 (2) Seg...117 (3) Seg...119 (4) Seg...120 (1)...122 (2)...122 (3) ( )...126 (1) (PCA)...127 (2) Draize...128 (1) Ames...129 2 in vitro...132
新入_本文.smd
52 28 220 28 4 1 017-777-1511 2 2 8 2 9 8 9 47.2% 12.8% 11.5% 6.0% 4 2 (49.6%)(13.0%) (14.7%) (7.4%)(8.4%) (52.3%)(9.1%) (11.4%) (10.0%) 33.0% 23.4% 15.6% 9.6% (26.0%) (18.3%) (46.5%) (30.0%) (20.0%) 2
国試過去問集.PDF
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外因性内分泌攪乱化学物質調査暫定マニュアル（水質、底質、水生生物）
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ORYZA CERAMIDE -PTPCDP8TP20CD -WSPWSP8 -LL0.8 -PCPC8PC20 -WSPCWSPC8 -LCLC0.8 Ver.13.0HS ORYZA CERAMIDE Ver.13.0HS 1. 2. 20 NMR 4 ( 1) 1 Ver.13.0HS HO CH 2 OH O O OH OH OH C CH CH H 2 NH C O R C H C H (CH
報告書 H22-2A-09
061-0293 1757 TEL 0133-23-1211 2.0% 0.5% in vitro QOL Quality of Life 1 MCE-400 400 mpa s Duck Algin 350M M/G 0.8 70 80 C 20% 50 C 1.0% 5 C SV-10 5 C 10 ml E TV 20H model E 1 34 R24 1 ml 5 C 30 6 12 30
エディロールカプセルインタビューフォーム
2012 4 5 873112 2008 () 1 0.5g 0.5g 0.75g 0.75g JAN EldecalcitolJAN 2011 1 21 2011 3 11 2011 4 11 TEL0120-591-818 03-3985-5599 8:3017:00 http://www.taishotoyama.co.jp/ 20124 http://www.info.pmda.go.jp/
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Ultron ES-VM : HPLC HPLC 28,000, 1-120Å 5-µm Ultron ES-VM [1-] Ultron ES-VM HPLC ph pi 3.8 4.3 Ultron ES-VM ph pi ph pka = 4.4 ph 3.0 6.0 pka = 4.0 9.2 k' 1 αph 1 Ibuprofen H3 C CHCH 2 CH CH H 3 C Chlorpheniramine
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50mg 75mg (1) H 3 C O OH HO H O O H OH SO H 3 Na H H N H 2 N NH OH H N O O H H O OH H 3 C H O O N H H H HO H NH CH 3 HN HO H OH O H OH H NH
3240 14 8 8 50mg 75mg 13 6 25 1-(1) H 3 C O OH HO H O O H OH SO H 3 Na H H N H 2 N NH OH H N O O H H O OH H 3 C H O O N H H H HO H NH CH 3 HN HO H OH O H OH H NH O N O C 56 H 70 N 9 NaO 23 S 1292.26 5-[(1S,2S)-2-
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1 20019 1527 CAS 1317368 1230 PbO 223.20 1 99 1. 2 888 2 9.53 0.017 g/l 20 3 3 2 2. 10 29,309 t 22,069 t 7,240 t 4 1 3. 1 2 3.5 6 1 µg/l 9.1-24 2 µg/l < 43 6 27,431-70,000 4.5-1,300 13.4-17 31.7 0.48-3,459
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1 9625 2219 CAS 75569 1, 2-1, 2- H 2 C CH CH 3 C 3 H 6 O 58.08 1 99 % 1. 2 2, 3-112.13 2, 3 34.23-37 449 2.8-37 % 2 d 0 4 0.859 4 d 20 0.8304 2 2, 4 2.00 = 1 53.33 kpa 400 mmhg18 59.33 kpa 445 mmhg20 5
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2 Zn Zn + MnO 2 () 2 O 2 2 H2 O + O 2 O 2 MnO 2 2 KClO 3 2 KCl + 3 O 2 O 3 or 3 O 2 2 O 3 N 2 () NH 4 NO 2 2 O + N 2 ( ) MnO HCl Mn O + CaCl(ClO
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3 57 210 57 JR 57325 132 28 IC JCT 28 4.1.1 4.1.1 4.1.2 4.1.2 4.1.1 11 35) 4.1.3 4.1.4 4.1.5 77 4.1.1 4.1.2 4.1.3 4.1.2 11 4.1.4 4.1.5 78 298 299 298 325 298 57 299 471 650 299 298 325 400m 640m 4.1.3
消防力適正配置調査報告
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1 982 2207 CAS 67630 2- H 3 C H 3 C CH OH C 3 H 8 O 60.10 1 99.9 % n- 1. 2-88.5 3 82.5 3 11.7c.c. 455 4 212 d 20 4 0.78505 3 2.1 = 1 4 4.4 kpa 33 mmhg20 4 log Pow0.05 0.07 5 m/z45, 1.0 43 0.19 27 0.17
取扱説明書
ED-601 ED-501 ED-401 2 3 4 23 14 5 6 18 10 7 1 2 6 3 4 8 9 16 16 16 12 1 2 18 10 2 1 5 12 11 1 2 1 2 12 1 2 13 16 14 3 2 4 1 1 2 16 3 4 18 15 1 2 16 2 3 1 1 2 3 18 17 18 22 19 D A C 20 A B 22 B C D 22
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ORYZA OIL & FAT CHEMICAL CO., LTD. ALPHA LIPOIC ACID --P () --P80 () --WSP8 () --L1 () --PC () --PC80 () --WSPC8 () --LC1 () ver. 5.1HS ver5.1 HS 1. ALPHA LIPOIC ACID 16 3 31 0331009 - () 19 5 24 0524001