;PMID: 12412639 ;source_file_1863.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..38] = [t:0..38] ;1)sentence:[e:44..154] = [t:44..154] ;2)section:[e:158..200] = [t:158..200] ;3)section:[e:204..266] = [t:204..266] ;4)sentence:[e:270..678] = [t:270..678] ;5)sentence:[e:679..762] = [t:679..762] ;6)sentence:[e:763..853] = [t:763..853] ;7)sentence:[e:854..1012] = [t:854..1012] ;8)sentence:[e:1013..1151] = [t:1013..1151] ;9)sentence:[e:1152..1347] = [t:1152..1347] ;10)section:[e:1351..1396] = [t:1351..1396] ;section 0 Span:0..38 ;Hum Exp Toxicol. 2002 Aug;21(8):453-6. (SEC (FRAG (NNP:[0..3] Hum) (NNP:[4..7] Exp) (NNP:[8..15] Toxicol) (.:[15..16] .) (CD:[17..21] 2002) (CC:[22..29] Aug;21-LRB-) (CD:[29..30] 8) (-RRB-:[30..31] -RRB-) (CD:[31..35] :453) (HYPH:[35..36] -) (CD:[36..38] 6.))) ;sentence 1 Span:44..154 ;A study of the in vitro clinical interaction between lidocaine and ;premedications using rat liver microsomes. ;[97..106]:substance:"lidocaine" (SENT (NP-HLN (NP (NP (DT:[44..45] A) (NN:[46..51] study)) (PP (IN:[52..54] of) (NP (NP (DT:[55..58] the) (ADJP (FW:[59..61] in) (FW:[62..67] vitro)) (JJ:[68..76] clinical) (NN:[77..88] interaction)) (PP (IN:[89..96] between) (NP (NN:[97..106] lidocaine) (CC:[107..110] and) (NNS:[112..126] premedications)))))) (VP (VBG:[127..132] using) (NP (NN:[133..136] rat) (NN:[137..142] liver) (NNS:[143..153] microsomes))) (.:[153..154] .))) ;section 2 Span:158..200 ;Nagashima A, Tanak E, Inomata S, Misawa S. (SEC (FRAG (NNP:[158..167] Nagashima) (NNP:[168..169] A) (,:[169..170] ,) (NNP:[171..176] Tanak) (NNP:[177..178] E) (,:[178..179] ,) (NNP:[180..187] Inomata) (NNP:[188..189] S) (,:[189..190] ,) (NNP:[191..197] Misawa) (NNP:[198..200] S.))) ;section 3 Span:204..266 ;Institute of Community Medicine, University of Tsukuba, Japan. (SEC (FRAG (NNP:[204..213] Institute) (IN:[214..216] of) (NNP:[217..226] Community) (NNP:[227..235] Medicine) (,:[235..236] ,) (NNP:[237..247] University) (IN:[248..250] of) (NNP:[251..258] Tsukuba) (,:[258..259] ,) (NNP:[260..265] Japan) (.:[265..266] .))) ;sentence 4 Span:270..678 ;In this study, we have investigated the relationship between lidocaine ;metabolism and premedication, i.e., psychotropic and anti-anxiety agents ;(diazepam, midazolam), hypnotics (pentobarbital, thiamylal), depolarizing ;muscular relaxants (vecuronium, pancuronium and suxamethonium), an active ;anti-hypertensive (clonidine) and an H2 receptor antagonist (cimetidine) ;using rat hepatic microsomes in vitro. ;[331..340]:substance:"lidocaine" ;[378..390]...[408..414]:substance:"psychotropic"..."agents" ;[395..414]:substance:"anti-anxiety agents" ;[417..425]:substance:"diazepam" ;[427..436]:substance:"midazolam" ;[439..448]:substance:"hypnotics" ;[450..463]:substance:"pentobarbital" ;[465..474]:substance:"thiamylal" ;[491..509]:substance:"muscular relaxants" ;[511..521]:substance:"vecuronium" ;[523..534]:substance:"pancuronium" ;[539..552]:substance:"suxamethonium" ;[566..583]:substance:"anti-hypertensive" ;[585..594]:substance:"clonidine" ;[603..614]:substance:"H2 receptor" ;[615..625]:substance:"antagonist" ;[627..637]:substance:"cimetidine" (SENT (S (PP (IN:[270..272] In) (NP (DT:[273..277] this) (NN:[278..283] study))) (,:[283..284] ,) (NP-SBJ (PRP:[285..287] we)) (VP (VBP:[288..292] have) (VP (VBN:[293..305] investigated) (NP (NP (DT:[306..309] the) (NN:[310..322] relationship)) (PP (IN:[323..330] between) (NP (NP (NN:[331..340] lidocaine) (NN:[342..352] metabolism)) (CC:[353..356] and) (NP (NP (NN:[357..370] premedication)) (,:[370..371] ,) (NP (ADVP (FW:[372..376] i.e.)) (,:[376..377] ,) (NP (NP (NP (JJ:[378..390] psychotropic) (NML-1 (-NONE-:[390..390] *P*))) (CC:[391..394] and) (NP (NML (AFX:[395..399] anti) (HYPH:[399..400] -) (NN:[400..407] anxiety)) (NML-1 (NNS:[408..414] agents)))) (NP (-LRB-:[416..417] -LRB-) (NN:[417..425] diazepam) (,:[425..426] ,) (NN:[427..436] midazolam) (-RRB-:[436..437] -RRB-))) (,:[437..438] ,) (NP (NP (NNS:[439..448] hypnotics)) (NP (-LRB-:[449..450] -LRB-) (NN:[450..463] pentobarbital) (,:[463..464] ,) (NN:[465..474] thiamylal) (-RRB-:[474..475] -RRB-))) (,:[475..476] ,) (NP (NP (VBG:[477..489] depolarizing) (JJ:[491..499] muscular) (NNS:[500..509] relaxants)) (NP (-LRB-:[510..511] -LRB-) (NN:[511..521] vecuronium) (,:[521..522] ,) (NN:[523..534] pancuronium) (CC:[535..538] and) (NN:[539..552] suxamethonium) (-RRB-:[552..553] -RRB-))) (,:[553..554] ,) (NP (NP (DT:[555..557] an) (JJ:[558..564] active) (AFX:[566..570] anti) (HYPH:[570..571] -) (JJ:[571..583] hypertensive)) (NP (-LRB-:[584..585] -LRB-) (NN:[585..594] clonidine) (-RRB-:[594..595] -RRB-))) (CC:[596..599] and) (NP (NP (DT:[600..602] an) (NML (NN:[603..605] H2) (NN:[606..614] receptor)) (NN:[615..625] antagonist)) (NP (-LRB-:[626..627] -LRB-) (NN:[627..637] cimetidine) (-RRB-:[637..638] -RRB-)))))))) (S-MNR (NP-SBJ (-NONE-:[638..638] *)) (VP (VBG:[639..644] using) (NP (NN:[646..649] rat) (JJ:[650..657] hepatic) (NNS:[658..668] microsomes)) (ADVP (FW:[669..671] in) (FW:[672..677] vitro)))))) (.:[677..678] .))) ;sentence 5 Span:679..762 ;Lidocaine metabolism was noncompetitively inhibited by midazolam (Ki=29.0 ;microM). ;[679..688]:substance:"Lidocaine" ;[735..744]:substance:"midazolam" ;[746..748]:quantitative-name:"Ki" ;[749..753]:quantitative-value:"29.0" ;[754..760]:quantitative-units:"microM" (SENT (S (NP-SBJ-1 (NN:[679..688] Lidocaine) (NN:[689..699] metabolism)) (VP (VBD:[700..703] was) (ADVP-MNR (RB:[704..720] noncompetitively)) (VP (VBN:[722..731] inhibited) (NP-1 (-NONE-:[731..731] *)) (PP (IN:[732..734] by) (NP-LGS (NN:[735..744] midazolam))) (PRN (-LRB-:[745..746] -LRB-) (S (NP-SBJ (NN:[746..748] Ki)) (VP (SYM:[748..749] =) (NP (CD:[749..753] 29.0) (NN:[754..760] microM)))) (-RRB-:[760..761] -RRB-)))) (.:[761..762] .))) ;sentence 6 Span:763..853 ;Thilamylal was a moderate competitive inhibitor of lidocaine metabolism ;(Ki=77.8 microM). ;[763..773]:substance:"Thilamylal" ;[802..811]:substance:"inhibitor" ;[815..824]:substance:"lidocaine" ;[837..839]:quantitative-name:"Ki" ;[840..844]:quantitative-value:"77.8" ;[845..851]:quantitative-units:"microM" (SENT (S (NP-SBJ (NN:[763..773] Thilamylal)) (VP (VBD:[774..777] was) (NP-PRD (NP (DT:[778..779] a) (JJ:[780..788] moderate) (JJ:[789..800] competitive) (NN:[802..811] inhibitor)) (PP (IN:[812..814] of) (NP (NN:[815..824] lidocaine) (NN:[825..835] metabolism)))) (PRN (-LRB-:[836..837] -LRB-) (S (NP-SBJ (NN:[837..839] Ki)) (VP (SYM:[839..840] =) (NP (CD:[840..844] 77.8) (NN:[845..851] microM)))) (-RRB-:[851..852] -RRB-))) (.:[852..853] .))) ;sentence 7 Span:854..1012 ;Pentobarbital, diazepam and cimetidine weakly inhibited lidocaine metabolism ;formation in a concentration-dependent manner at high substrate ;concentrations. ;[854..867]:substance:"Pentobarbital" ;[869..877]:substance:"diazepam" ;[883..893]:substance:"cimetidine" ;[911..920]:substance:"lidocaine" ;[987..996]:substance:"substrate" (SENT (S (NP-SBJ (NN:[854..867] Pentobarbital) (,:[867..868] ,) (NN:[869..877] diazepam) (CC:[878..881] and) (NN:[883..893] cimetidine)) (ADVP (RB:[894..900] weakly)) (VP (VBD:[901..910] inhibited) (NP (NML (NN:[911..920] lidocaine) (NN:[921..931] metabolism)) (NN:[932..941] formation)) (PP (IN:[942..944] in) (NP (DT:[945..946] a) (ADJP (NN:[948..961] concentration) (HYPH:[961..962] -) (JJ:[962..971] dependent)) (NN:[972..978] manner))) (PP (IN:[979..981] at) (NP (JJ:[982..986] high) (NN:[987..996] substrate) (NNS:[997..1011] concentrations)))) (.:[1011..1012] .))) ;sentence 8 Span:1013..1151 ;On the other hand, vecuronium, pancuronium, suxamethonium and clonidine did ;not inhibit lidocaine metabolism over the therapeutic range. ;[1033..1043]:substance:"vecuronium" ;[1045..1056]:substance:"pancuronium" ;[1058..1071]:substance:"suxamethonium" ;[1076..1085]:substance:"clonidine" ;[1103..1112]:substance:"lidocaine" (SENT (S (PP (IN:[1013..1015] On) (NP (DT:[1016..1019] the) (JJ:[1020..1025] other) (NN:[1027..1031] hand))) (,:[1031..1032] ,) (NP-SBJ (NN:[1033..1043] vecuronium) (,:[1043..1044] ,) (NN:[1045..1056] pancuronium) (,:[1056..1057] ,) (NN:[1058..1071] suxamethonium) (CC:[1072..1075] and) (NN:[1076..1085] clonidine)) (VP (VBD:[1086..1089] did) (RB:[1090..1093] not) (VP (VB:[1094..1101] inhibit) (NP (NN:[1103..1112] lidocaine) (NN:[1113..1123] metabolism)) (PP (IN:[1124..1128] over) (NP (DT:[1129..1132] the) (JJ:[1133..1144] therapeutic) (NN:[1145..1150] range))))) (.:[1150..1151] .))) ;sentence 9 Span:1152..1347 ;These results show that the interaction between lidocaine and midazolam and ;thiamylal, catalyzed by a similar cytochrome P450, is of potential ;importance in toxicological and clinical studies. ;[1201..1210]:substance:"lidocaine" ;[1215..1224]:substance:"midazolam" ;[1229..1238]:substance:"thiamylal" ;[1264..1279]:cyp450:"cytochrome P450" (SENT (S (NP-SBJ (DT:[1152..1157] These) (NNS:[1158..1165] results)) (VP (VBP:[1166..1170] show) (SBAR (IN:[1171..1175] that) (S (NP-SBJ (NP (NP (DT:[1176..1179] the) (NN:[1181..1192] interaction)) (PP (IN:[1193..1200] between) (NP (NP (NN:[1201..1210] lidocaine)) (CC:[1211..1214] and) (NP (NN:[1215..1224] midazolam) (CC:[1225..1228] and) (NN:[1229..1238] thiamylal))))) (,:[1238..1239] ,) (VP (VBN:[1240..1249] catalyzed) (NP (-NONE-:[1249..1249] *)) (PP (IN:[1250..1252] by) (NP-LGS (DT:[1253..1254] a) (JJ:[1256..1263] similar) (NN:[1264..1274] cytochrome) (NN:[1275..1279] P450))))) (,:[1279..1280] ,) (VP (VBZ:[1281..1283] is) (PP-PRD (IN:[1284..1286] of) (NP (JJ:[1287..1296] potential) (NN:[1297..1307] importance))) (PP (IN:[1308..1310] in) (NP (NP (JJ:[1311..1324] toxicological) (NML-1 (-NONE-:[1324..1324] *P*))) (CC:[1325..1328] and) (NP (JJ:[1330..1338] clinical) (NML-1 (NNS:[1339..1346] studies))))))))) (.:[1346..1347] .))) ;section 10 Span:1351..1396 ;PMID: 12412639 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1351..1355] PMID) (::[1355..1356] :) (CD:[1357..1365] 12412639) (NN:[1366..1367] -LSB-) (NNP:[1367..1373] PubMed) (::[1374..1375] -) (NN:[1376..1383] indexed) (IN:[1384..1387] for) (NNP:[1388..1396] MEDLINE-RSB-)))