;PMID: 4035074 ;source_file_1003.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..56] = [t:0..56] ;1)sentence:[e:62..117] = [t:62..117] ;2)section:[e:121..138] = [t:121..138] ;3)sentence:[e:142..232] = [t:142..232] ;4)sentence:[e:233..390] = [t:233..390] ;5)sentence:[e:391..465] = [t:391..465] ;6)sentence:[e:466..626] = [t:466..626] ;7)sentence:[e:627..855] = [t:627..855] ;8)sentence:[e:856..1009] = [t:856..1009] ;9)sentence:[e:1010..1130] = [t:1010..1130] ;10)sentence:[e:1131..1262] = [t:1131..1262] ;11)section:[e:1266..1310] = [t:1266..1310] ;section 0 Span:0..56 ;Res Commun Chem Pathol Pharmacol. 1985 Jul;49(1):109-24. (SEC (FRAG (NNP:[0..3] Res) (NNP:[4..10] Commun) (NNP:[11..15] Chem) (NNP:[16..22] Pathol) (NNP:[23..32] Pharmacol) (.:[32..33] .) (CD:[34..38] 1985) (::[39..46] Jul;49-LRB-) (CD:[46..47] 1) (-RRB-:[47..48] -RRB-) (CD:[48..52] :109) (::[52..53] -) (CD:[53..55] 24) (.:[55..56] .))) ;sentence 1 Span:62..117 ;Kinetics of microsomal metabolism of quinidine in rats. ;[99..108]:substance:"quinidine" (SENT (NP-HLN (NP (NN:[62..70] Kinetics)) (PP (IN:[71..73] of) (NP (NP (JJ:[74..84] microsomal) (NN:[85..95] metabolism)) (PP (IN:[96..98] of) (NP (NN:[99..108] quinidine))) (PP-LOC (IN:[109..111] in) (NP (NNS:[112..116] rats))))) (.:[116..117] .))) ;section 2 Span:121..138 ;Rakhit A, Mico B. (SEC (FRAG (NNP:[121..127] Rakhit) (NNP:[128..129] A) (,:[129..130] ,) (NNP:[131..135] Mico) (NNP:[136..138] B.))) ;sentence 3 Span:142..232 ;Kinetics of in vitro metabolism of quinidine was investigated using rat liver ; microsomes. ;[177..186]:substance:"quinidine" (SENT (S (NP-SBJ-1 (NP (NN:[142..150] Kinetics)) (PP (IN:[151..153] of) (NP (NP (ADJP (FW:[154..156] in) (FW:[157..162] vitro)) (NN:[163..173] metabolism)) (PP (IN:[174..176] of) (NP (NN:[177..186] quinidine)))))) (VP (VBD:[187..190] was) (VP (VBN:[191..203] investigated) (NP-1 (-NONE-:[203..203] *)) (S-MNR (NP-SBJ (-NONE-:[203..203] *)) (VP (VBG:[204..209] using) (NP (NN:[210..213] rat) (NN:[214..219] liver) (NNS:[221..231] microsomes)))))) (.:[231..232] .))) ;sentence 4 Span:233..390 ;Quinidine elimination was capacity limited with apparent Michaelis constant ;(appKM) of 2.6 microM (about 1.2 mg/L) in liver microsomes from uninduced ;rats. ;[233..242]:substance:"Quinidine" ;[311..316]:quantitative-name:"appKM" ;[321..324]:quantitative-value:"2.6" ;[325..331]:quantitative-units:"microM" ;[339..342]:quantitative-value:"1.2" ;[343..347]:quantitative-units:"mg/L" (SENT (S (NP-SBJ-1 (NN:[233..242] Quinidine) (NN:[243..254] elimination)) (VP (VBD:[255..258] was) (NP-ADV (NN:[259..267] capacity)) (VP (VBN:[268..275] limited) (NP-1 (-NONE-:[275..275] *)) (PP (IN:[276..280] with) (NP (NP (NP (JJ:[281..289] apparent) (NNP:[290..299] Michaelis) (NN:[301..309] constant)) (NP (-LRB-:[310..311] -LRB-) (NN:[311..316] appKM) (-RRB-:[316..317] -RRB-))) (PP (IN:[318..320] of) (NP (CD:[321..324] 2.6) (NN:[325..331] microM) (PRN (-LRB-:[332..333] -LRB-) (NP (NP (QP (RB:[333..338] about) (CD:[339..342] 1.2)) (NN:[343..345] mg)) (PP (SYM:[345..346] /) (NP (NN:[346..347] L)))) (-RRB-:[347..348] -RRB-)))))) (PP-LOC (IN:[349..351] in) (NP (NP (NN:[352..357] liver) (NNS:[358..368] microsomes)) (PP (IN:[369..373] from) (NP (JJ:[375..384] uninduced) (NNS:[385..389] rats))))))) (.:[389..390] .))) ;sentence 5 Span:391..465 ;Phenobarbital (PB) pretreatment caused induction of quinidine metabolism. ;[391..404]:substance:"Phenobarbital" ;[406..408]:substance:"PB" ;[443..452]:substance:"quinidine" (SENT (S (NP-SBJ (NML (NML (NN:[391..404] Phenobarbital)) (NML (-LRB-:[405..406] -LRB-) (NN:[406..408] PB) (-RRB-:[408..409] -RRB-))) (NN:[410..422] pretreatment)) (VP (VBD:[423..429] caused) (NP (NP (NN:[430..439] induction)) (PP (IN:[440..442] of) (NP (NN:[443..452] quinidine) (NN:[454..464] metabolism))))) (.:[464..465] .))) ;sentence 6 Span:466..626 ;Formation of all three metabolites important in man, 3-hydroxyquinidine, ;quinidine N-oxide and quinidine 10,11-dihydrodiol were PB inducible (Vmax ;increased). ;[489..500]:substance:"metabolites" ;[520..538]:substance:"3-hydroxyquinidine" ;[540..557]:substance:"quinidine N-oxide" ;[562..589]:substance:"quinidine 10,11-dihydrodiol" ;[595..597]:substance:"PB" ;[610..614]:quantitative-name:"Vmax" (SENT (S (NP-SBJ (NP (NN:[466..475] Formation)) (PP (IN:[476..478] of) (NP (NP (NP (DT:[479..482] all) (CD:[483..488] three) (NNS:[489..500] metabolites)) (ADJP (JJ:[501..510] important) (PP (IN:[511..513] in) (NP (NN:[514..517] man))))) (,:[517..518] ,) (NP (NP (NN:[520..538] 3-hydroxyquinidine)) (,:[538..539] ,) (NP (NN:[540..549] quinidine) (NN:[550..557] N-oxide)) (CC:[558..561] and) (NP (NN:[562..571] quinidine) (NN:[572..589] 10,11-dihydrodiol)))))) (VP (VBD:[590..594] were) (ADJP-PRD (NN:[595..597] PB) (JJ:[599..608] inducible) (PRN (-LRB-:[609..610] -LRB-) (S (NP-SBJ (NN:[610..614] Vmax)) (VP (VBD:[615..624] increased))) (-RRB-:[624..625] -RRB-)))) (.:[625..626] .))) ;sentence 7 Span:627..855 ;To study any direct interaction between PB and quinidine, PB was also added ;to the microsomal incubate and was found to decrease the rate constant for ;quinidine metabolism, suggesting inhibition of quinidine metabolism by PB. ;[667..669]:substance:"PB" ;[675..684]:substance:"quinidine" ;[686..688]:substance:"PB" ;[780..789]:substance:"quinidine" ;[828..837]:substance:"quinidine" ;[852..854]:substance:"PB" (SENT (S (S-PRP (NP-SBJ (-NONE-:[627..627] *)) (VP (TO:[627..629] To) (VP (VB:[630..635] study) (NP (NP (DT:[636..639] any) (JJ:[640..646] direct) (NN:[647..658] interaction)) (PP (IN:[659..666] between) (NP (NN:[667..669] PB) (CC:[670..673] and) (NN:[675..684] quinidine))))))) (,:[684..685] ,) (NP-SBJ-1 (NN:[686..688] PB)) (VP (VP (VBD:[689..692] was) (ADVP (RB:[693..697] also)) (VP (VBN:[698..703] added) (NP-1 (-NONE-:[703..703] *)) (PP (TO:[704..706] to) (NP (DT:[707..710] the) (JJ:[711..721] microsomal) (NN:[722..730] incubate))))) (CC:[731..734] and) (VP (VBD:[735..738] was) (VP (VBN:[739..744] found) (S (NP-SBJ-1 (-NONE-:[744..744] *)) (VP (TO:[745..747] to) (VP (VB:[749..757] decrease) (NP (NP (DT:[758..761] the) (NN:[762..766] rate) (NN:[767..775] constant)) (PP (IN:[776..779] for) (NP (NN:[780..789] quinidine) (NN:[790..800] metabolism)))) (,:[800..801] ,) (S-ADV (NP-SBJ (-NONE-:[801..801] *)) (VP (VBG:[802..812] suggesting) (NP (NP (NN:[813..823] inhibition)) (PP (IN:[824..826] of) (NP (NN:[828..837] quinidine) (NN:[838..848] metabolism))) (PP (IN:[849..851] by) (NP (NN:[852..854] PB)))))))))))) (.:[854..855] .))) ;sentence 8 Span:856..1009 ;While, 3-hydroxyquinidine formation was inhibited (Vmax decreased and KM ;increased), the formation of quinidine N-oxide was activated (Vmax ;increased). ;[863..881]:substance:"3-hydroxyquinidine" ;[908..912]:quantitative-name:"Vmax" ;[927..929]:quantitative-name:"KM" ;[959..976]:substance:"quinidine N-oxide" ;[993..997]:quantitative-name:"Vmax" (SENT (S (SBAR-ADV (IN:[856..861] While) (.:[861..862] ,) (S (NP-SBJ-1 (NN:[863..881] 3-hydroxyquinidine) (NN:[882..891] formation)) (VP (VBD:[892..895] was) (VP (VBN:[896..905] inhibited) (NP-1 (-NONE-:[905..905] *)) (PRN (-LRB-:[907..908] -LRB-) (S (S (NP-SBJ (NN:[908..912] Vmax)) (VP (VBD:[913..922] decreased))) (CC:[923..926] and) (S (NP-SBJ (NN:[927..929] KM)) (VP (VBD:[930..939] increased)))) (-RRB-:[939..940] -RRB-)))))) (,:[940..941] ,) (NP-SBJ-2 (NP (DT:[942..945] the) (NN:[946..955] formation)) (PP (IN:[956..958] of) (NP (NN:[959..968] quinidine) (NN:[969..976] N-oxide)))) (VP (VBD:[977..980] was) (VP (VBN:[982..991] activated) (NP-2 (-NONE-:[991..991] *)) (PRN (-LRB-:[992..993] -LRB-) (S (NP-SBJ (NN:[993..997] Vmax)) (VP (VBD:[998..1007] increased))) (-RRB-:[1007..1008] -RRB-)))) (.:[1008..1009] .))) ;sentence 9 Span:1010..1130 ;The formation of quinidine 10,11-dihydrodiol, although a minor metabolite in ;rat, was also inhibited in presence of PB. ;[1027..1054]:substance:"quinidine 10,11-dihydrodiol" ;[1074..1084]:substance:"metabolite" ;[1127..1129]:substance:"PB" (SENT (S (NP-SBJ-1 (NP (DT:[1010..1013] The) (NN:[1014..1023] formation)) (PP (IN:[1024..1026] of) (NP (NP (NN:[1027..1036] quinidine) (NN:[1037..1054] 10,11-dihydrodiol)) (FRAG (,:[1054..1055] ,) (IN:[1057..1065] although) (NP (NP (DT:[1066..1067] a) (JJ:[1068..1073] minor) (NN:[1074..1084] metabolite)) (PP (IN:[1085..1087] in) (NP (NN:[1088..1091] rat)))) (,:[1091..1092] ,))))) (VP (VBD:[1093..1096] was) (ADVP (RB:[1097..1101] also)) (VP (VBN:[1102..1111] inhibited) (NP-1 (-NONE-:[1111..1111] *)) (PP (IN:[1112..1114] in) (NP (NP (NN:[1115..1123] presence)) (PP (IN:[1124..1126] of) (NP (NN:[1127..1129] PB))))))) (.:[1129..1130] .))) ;sentence 10 Span:1131..1262 ;It is apparent from this study that PB when administered in vivo would act ;as both inducer and inhibitor of quinidine metabolism. ;[1168..1170]:substance:"PB" ;[1216..1223]:substance:"inducer" ;[1228..1237]:substance:"inhibitor" ;[1241..1250]:substance:"quinidine" (SENT (S (NP-SBJ (PRP:[1131..1133] It)) (VP (VBZ:[1134..1136] is) (ADJP-PRD (JJ:[1138..1146] apparent) (PP (IN:[1147..1151] from) (NP (DT:[1152..1156] this) (NN:[1157..1162] study))) (SBAR (IN:[1163..1167] that) (S (NP-SBJ (NN:[1168..1170] PB)) (SBAR-ADV (IN:[1171..1175] when) (S (NP-SBJ-2 (-NONE-:[1175..1175] *)) (VP (VBN:[1176..1188] administered) (NP-2 (-NONE-:[1188..1188] *)) (ADVP (FW:[1189..1191] in) (FW:[1192..1196] vivo))))) (VP (MD:[1197..1202] would) (VP (VB:[1203..1206] act) (PP (IN:[1207..1209] as) (NP (NP (CC:[1210..1214] both) (NN:[1216..1223] inducer) (CC:[1224..1227] and) (NN:[1228..1237] inhibitor)) (PP (IN:[1238..1240] of) (NP (NN:[1241..1250] quinidine) (NN:[1251..1261] metabolism))))))))))) (.:[1261..1262] .))) ;section 11 Span:1266..1310 ;PMID: 4035074 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1266..1270] PMID) (::[1270..1271] :) (CD:[1272..1279] 4035074) (NN:[1280..1281] -LSB-) (NNP:[1281..1287] PubMed) (::[1288..1289] -) (NN:[1290..1297] indexed) (IN:[1298..1301] for) (NNP:[1302..1310] MEDLINE-RSB-)))