;PMID: 2638529 ;source_file_1890.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..42] = [t:0..42] ;1)sentence:[e:48..112] = [t:48..112] ;2)section:[e:116..144] = [t:116..144] ;3)section:[e:148..240] = [t:148..240] ;4)sentence:[e:244..375] = [t:244..375] ;5)sentence:[e:376..538] = [t:376..538] ;6)sentence:[e:539..700] = [t:539..700] ;7)sentence:[e:701..880] = [t:701..880] ;8)sentence:[e:881..1101] = [t:881..1101] ;9)sentence:[e:1103..1281] = [t:1103..1281] ;10)sentence:[e:1282..1427] = [t:1282..1427] ;11)sentence:[e:1428..1664] = [t:1428..1664] ;12)section:[e:1668..1712] = [t:1668..1712] ;section 0 Span:0..42 ;Trans Assoc Am Physicians. 1989;102:44-54. (SEC (FRAG (FRAG (NNP:[0..5] Trans) (NNP:[6..11] Assoc) (NNP:[12..14] Am) (NNP:[15..25] Physicians) (.:[25..26] .) (CD:[27..31] 1989) (CD:[31..35] ;102) (CD:[35..38] :44) (CD:[38..41] -54) (.:[41..42] .)))) ;sentence 1 Span:48..112 ;The oxidative metabolism of estradiol: inhibition by cimetidine. ;[76..85]:substance:"estradiol" ;[101..111]:substance:"cimetidine" (SENT (NP-HLN (NP (NP (DT:[48..51] The) (JJ:[52..61] oxidative) (NN:[62..72] metabolism)) (PP (IN:[73..75] of) (NP (NN:[76..85] estradiol)))) (::[85..86] :) (NP (NP (NN:[87..97] inhibition)) (PP (IN:[98..100] by) (NP (NN:[101..111] cimetidine)))) (.:[111..112] .))) ;section 2 Span:116..144 ;Galbraith RA, Michnovicz JJ. (SEC (FRAG (NNP:[116..125] Galbraith) (NNP:[126..128] RA) (,:[128..129] ,) (NNP:[130..140] Michnovicz) (NNP:[141..144] JJ.))) ;section 3 Span:148..240 ;Department of Metabolism-Pharmacology, Rockefeller University Hospital, New ;York, NY 10021. (SEC (FRAG (NNP:[148..158] Department) (IN:[159..161] of) (NNP:[162..172] Metabolism) (HYPH:[172..173] -) (NNP:[173..185] Pharmacology) (,:[185..186] ,) (NNP:[187..198] Rockefeller) (NNP:[199..209] University) (NNP:[210..218] Hospital) (,:[218..219] ,) (NNP:[220..223] New) (NNP:[225..229] York) (,:[229..230] ,) (NNP:[231..233] NY) (CD:[234..239] 10021) (.:[239..240] .))) ;sentence 4 Span:244..375 ;Cimetidine, a histamine H2 antagonist, is known to interfere with the ;metabolism of exogenous drugs by binding to cytochrome P450. ;[244..254]:substance:"Cimetidine" ;[258..270]:substance:"histamine H2" ;[271..281]:substance:"antagonist" ;[339..344]:substance:"drugs" ;[359..374]:cyp450:"cytochrome P450" (SENT (S (NP-SBJ-1 (NP (NN:[244..254] Cimetidine)) (,:[254..255] ,) (NP (DT:[256..257] a) (NN:[258..267] histamine) (NN:[268..270] H2) (NN:[271..281] antagonist))) (,:[281..282] ,) (VP (VBZ:[283..285] is) (VP (VBN:[286..291] known) (S (NP-SBJ-1 (-NONE-:[291..291] *)) (VP (TO:[292..294] to) (VP (VB:[295..304] interfere) (PP (IN:[305..309] with) (NP (NP (DT:[310..313] the) (NN:[314..324] metabolism)) (PP (IN:[326..328] of) (NP (JJ:[329..338] exogenous) (NNS:[339..344] drugs))))) (PP-MNR (IN:[345..347] by) (S-NOM (NP-SBJ (-NONE-:[347..347] *)) (VP (VBG:[348..355] binding) (PP (TO:[356..358] to) (NP (NN:[359..369] cytochrome) (NN:[370..374] P450))))))))))) (.:[374..375] .))) ;sentence 5 Span:376..538 ;We examined the possibility that cimetidine might also inhibit the ;cytochrome P450-dependent biotransformation of endogenous compounds such as ;steroid hormones. ;[410..420]:substance:"cimetidine" ;[444..459]:cyp450:"cytochrome P450" ;[503..512]:substance:"compounds" ;[521..537]:substance:"steroid hormones" (SENT (S (NP-SBJ (PRP:[376..378] We)) (VP (VBD:[379..387] examined) (NP (DT:[388..391] the) (NN:[392..403] possibility) (SBAR (IN:[405..409] that) (S (NP-SBJ (NN:[410..420] cimetidine)) (VP (MD:[421..426] might) (ADVP (RB:[427..431] also)) (VP (VB:[432..439] inhibit) (NP (NP (DT:[440..443] the) (ADJP (NML (NN:[444..454] cytochrome) (NN:[455..459] P450)) (HYPH:[459..460] -) (JJ:[460..469] dependent)) (NN:[471..488] biotransformation)) (PP (IN:[489..491] of) (NP (NP (JJ:[492..502] endogenous) (NNS:[503..512] compounds)) (PP (JJ:[513..517] such) (IN:[518..520] as) (NP (JJ:[521..528] steroid) (NNS:[529..537] hormones)))))))))))) (.:[537..538] .))) ;sentence 6 Span:539..700 ;Utilizing a radiometric assay and normal male volunteers, the acute effect ;of intravenous cimetidine (300 mg loading dose followed by 50 mg/hr) was ;determined. ;[631..641]:substance:"cimetidine" ;[643..646]:quantitative-value:"300" ;[647..649]:quantitative-units:"mg" ;[675..677]:quantitative-value:"50" ;[678..683]:quantitative-units:"mg/hr" (SENT (S (S-MNR (NP-SBJ (-NONE-:[539..539] *)) (VP (VBG:[539..548] Utilizing) (NP (NP (DT:[549..550] a) (JJ:[552..563] radiometric) (NN:[564..569] assay)) (CC:[570..573] and) (NP (JJ:[574..580] normal) (JJ:[581..585] male) (NNS:[586..596] volunteers))))) (,:[596..597] ,) (NP-SBJ-1 (NP (DT:[598..601] the) (JJ:[602..607] acute) (NN:[608..614] effect)) (PP (IN:[615..617] of) (NP (NP (JJ:[618..629] intravenous) (NN:[631..641] cimetidine)) (PRN (-LRB-:[642..643] -LRB-) (NP (NP (NML (CD:[643..646] 300) (NN:[647..649] mg)) (VBG:[650..657] loading) (NN:[658..662] dose)) (VP (VBN:[663..671] followed) (NP (-NONE-:[671..671] *)) (PP (IN:[672..674] by) (NP-LGS (NP (CD:[675..677] 50) (NN:[678..680] mg)) (PP (SYM:[680..681] /) (NP (NN:[681..683] hr))))))) (-RRB-:[683..684] -RRB-))))) (VP (VBD:[685..688] was) (VP (VBN:[689..699] determined) (NP-1 (-NONE-:[699..699] *)))) (.:[699..700] .))) ;sentence 7 Span:701..880 ;The extent of 2-hydroxylation of estradiol was reduced by 25% from 29.6 +/- ;4.4% (mean +/- SEM) before, to 22.9 +/- 4.0% during cimetidine infusion (n = ;8; p less than 0.0005). ;[735..744]:substance:"estradiol" ;[760..763]:quantitative-value:"25%" ;[769..782]:quantitative-value:"29.6 +/- 4.4%" ;[810..823]:quantitative-value:"22.9 +/- 4.0%" ;[831..841]:substance:"cimetidine" (SENT (S (NP-SBJ-2 (NP (DT:[701..704] The) (NN:[705..711] extent)) (PP (IN:[713..715] of) (NP (NP (NN:[716..731] 2-hydroxylation)) (PP (IN:[732..734] of) (NP (NN:[735..744] estradiol)))))) (VP (VBD:[745..748] was) (VP (VBN:[749..756] reduced) (NP-2 (-NONE-:[756..756] *)) (PP-EXT (IN:[757..759] by) (NP (CD:[760..762] 25) (NN:[762..763] %))) (PP (IN:[764..768] from) (NP (NP (QP (CD:[769..773] 29.6) (SYM:[774..777] +/-) (CD:[778..781] 4.4)) (NN:[781..782] %)) (PRN (-LRB-:[783..784] -LRB-) (S (NP-SBJ (NN:[784..788] mean)) (VP (SYM:[789..792] +/-) (NP (NN:[794..797] SEM)))) (-RRB-:[797..798] -RRB-)) (PP-TMP (IN:[799..805] before) (NP-1 (-NONE-:[805..805] *RNR*))))) (,:[805..806] ,) (PP (TO:[807..809] to) (NP (NP (QP (CD:[810..814] 22.9) (SYM:[815..818] +/-) (CD:[819..822] 4.0)) (NN:[822..823] %)) (PP-TMP (IN:[824..830] during) (NP-1 (-NONE-:[830..830] *RNR*))))) (NP-1 (NN:[831..841] cimetidine) (NN:[842..850] infusion)) (PRN (-LRB-:[851..852] -LRB-) (S (S (NP-SBJ (NN:[852..853] n)) (VP (SYM:[854..855] =) (NP (CD:[856..857] 8)))) (::[857..858] ;) (S (NP-SBJ (NN:[859..860] p)) (ADJP-PRD (JJR:[861..865] less) (PP (IN:[866..870] than) (NP (CD:[872..878] 0.0005)))))) (-RRB-:[878..879] -RRB-)))) (.:[879..880] .))) ;sentence 8 Span:881..1101 ;Following oral cimetidine (800 mg b.i.d.) for 2 wk, estradiol ;2-hydroxylation was decreased by 40% from 31.7 +/- 2.3% to 19.7 +/- 2.4% (n = ;9; p less than 0.0001) but 16 alpha-hydroxylation of estradiol was ;unaffected. ;[896..906]:substance:"cimetidine" ;[908..911]:quantitative-value:"800" ;[912..914]:quantitative-units:"mg" ;[927..928]:quantitative-value:"2" ;[929..931]:quantitative-units:"wk" ;[933..942]:substance:"estradiol" ;[977..980]:quantitative-value:"40%" ;[986..999]:quantitative-value:"31.7 +/- 2.3%" ;[1003..1016]:quantitative-value:"19.7 +/- 2.4%" ;[1076..1085]:substance:"estradiol" (SENT (S (S-ADV (NP-SBJ (-NONE-:[881..881] *)) (VP (VBG:[881..890] Following) (NP (NP (JJ:[891..895] oral) (NN:[896..906] cimetidine)) (PRN (-LRB-:[907..908] -LRB-) (FRAG (NP (CD:[908..911] 800) (NN:[912..914] mg)) (ADJP (RB:[915..921] b.i.d.))) (-RRB-:[921..922] -RRB-))) (PP-TMP (IN:[923..926] for) (NP (CD:[927..928] 2) (NN:[929..931] wk))))) (,:[931..932] ,) (S (NP-SBJ-2 (NN:[933..942] estradiol) (NN:[944..959] 2-hydroxylation)) (VP (VBD:[960..963] was) (VP (VBN:[964..973] decreased) (NP-2 (-NONE-:[973..973] *)) (PP-EXT (IN:[974..976] by) (NP (CD:[977..979] 40) (NN:[979..980] %))) (PP (IN:[981..985] from) (NP (QP (CD:[986..990] 31.7) (SYM:[991..994] +/-) (CD:[995..998] 2.3)) (NN:[998..999] %))) (PP (TO:[1000..1002] to) (NP (QP (CD:[1003..1007] 19.7) (SYM:[1008..1011] +/-) (CD:[1012..1015] 2.4)) (NN:[1015..1016] %))) (PRN (-LRB-:[1017..1018] -LRB-) (S (S (NP-SBJ (NN:[1018..1019] n)) (VP (SYM:[1020..1021] =) (NP (CD:[1022..1023] 9)))) (::[1023..1024] ;) (S (NP-SBJ (NN:[1026..1027] p)) (ADJP-PRD (JJR:[1028..1032] less) (PP (IN:[1033..1037] than) (NP (CD:[1038..1044] 0.0001)))))) (-RRB-:[1044..1045] -RRB-))))) (CC:[1046..1049] but) (S (NP-SBJ-1 (NP (CD:[1050..1052] 16) (NN:[1053..1072] alpha-hydroxylation)) (PP (IN:[1073..1075] of) (NP (NN:[1076..1085] estradiol)))) (VP (VBD:[1086..1089] was) (VP (JJ:[1090..1100] unaffected) (NP-1 (-NONE-:[1100..1100] *))))) (.:[1100..1101] .))) ;sentence 9 Span:1103..1281 ;Concomitantly, the urinary excretion of 2-hydroxyestrone was decreased by 25% ;(p less than 0.002) and the serum estradiol concentration was increased by ;20% (p less than 0.04). ;[1143..1159]:substance:"2-hydroxyestrone" ;[1177..1180]:quantitative-value:"25%" ;[1216..1225]:substance:"estradiol" ;[1257..1260]:quantitative-value:"20%" (SENT (S (ADVP-TMP (RB:[1103..1116] Concomitantly)) (,:[1116..1117] ,) (S (NP-SBJ-2 (NP (DT:[1118..1121] the) (JJ:[1122..1129] urinary) (NN:[1130..1139] excretion)) (PP (IN:[1140..1142] of) (NP (NN:[1143..1159] 2-hydroxyestrone)))) (VP (VBD:[1160..1163] was) (VP (VBN:[1164..1173] decreased) (NP-2 (-NONE-:[1173..1173] *)) (PP-EXT (IN:[1174..1176] by) (NP (CD:[1177..1179] 25) (NN:[1179..1180] %)))) (PRN (-LRB-:[1181..1182] -LRB-) (S (NP-SBJ (NN:[1182..1183] p)) (ADJP-PRD (JJR:[1185..1189] less) (PP (IN:[1190..1194] than) (NP (CD:[1195..1200] 0.002))))) (-RRB-:[1200..1201] -RRB-)))) (CC:[1202..1205] and) (S (NP-SBJ-1 (DT:[1206..1209] the) (NN:[1210..1215] serum) (NN:[1216..1225] estradiol) (NN:[1226..1239] concentration)) (VP (VBD:[1240..1243] was) (VP (VBN:[1244..1253] increased) (NP-1 (-NONE-:[1253..1253] *)) (PP-EXT (IN:[1254..1256] by) (NP (CD:[1257..1259] 20) (NN:[1259..1260] %))) (PRN (-LRB-:[1261..1262] -LRB-) (S (NP-SBJ (NN:[1262..1263] p)) (ADJP-PRD (JJR:[1265..1269] less) (PP (IN:[1270..1274] than) (NP (CD:[1275..1279] 0.04))))) (-RRB-:[1279..1280] -RRB-))))) (.:[1280..1281] .))) ;sentence 10 Span:1282..1427 ;In contrast, ranitidine, a second generation H2 receptor antagonist, had no ;effect on estradiol hydroxylation following 150 mg b.i.d. for 2 wk. ;[1295..1305]:substance:"ranitidine" ;[1327..1338]:substance:"H2 receptor" ;[1340..1350]:substance:"antagonist" ;[1369..1378]:substance:"estradiol" ;[1403..1406]:quantitative-value:"150" ;[1407..1409]:quantitative-units:"mg" ;[1422..1423]:quantitative-value:"2" ;[1424..1426]:quantitative-units:"wk" (SENT (S (PP (IN:[1282..1284] In) (NP (NN:[1285..1293] contrast))) (,:[1293..1294] ,) (NP-SBJ (NP (NN:[1295..1305] ranitidine)) (,:[1305..1306] ,) (NP (DT:[1307..1308] a) (NML (JJ:[1309..1315] second) (NN:[1316..1326] generation)) (NN:[1327..1329] H2) (NN:[1330..1338] receptor) (NN:[1340..1350] antagonist))) (,:[1350..1351] ,) (VP (VBD:[1352..1355] had) (NP (DT:[1356..1358] no) (NN:[1359..1365] effect)) (PP (IN:[1366..1368] on) (NP (NN:[1369..1378] estradiol) (NN:[1379..1392] hydroxylation))) (S-ADV (NP-SBJ (-NONE-:[1392..1392] *)) (VP (VBG:[1393..1402] following) (NP (NP (CD:[1403..1406] 150) (NN:[1407..1409] mg)) (ADJP (RB:[1410..1416] b.i.d.))) (PP (IN:[1417..1420] for) (NP (CD:[1422..1423] 2) (NN:[1424..1426] wk)))))) (.:[1426..1427] .))) ;sentence 11 Span:1428..1664 ;The inhibition of estradiol 2-hydroxylation and the increase in serum ;estradiol concentrations caused by cimetidine administration may help to ;account for the symptoms of hyperestrogenization reported in long-term ;cimetidine therapy. ;[1446..1455]:substance:"estradiol" ;[1499..1508]:substance:"estradiol" ;[1534..1544]:substance:"cimetidine" ;[1644..1654]:substance:"cimetidine" (SENT (S (NP-SBJ (NP (NP (NP (DT:[1428..1431] The) (NN:[1432..1442] inhibition)) (PP (IN:[1443..1445] of) (NP (NN:[1446..1455] estradiol) (NN:[1456..1471] 2-hydroxylation)))) (CC:[1472..1475] and) (NP (NP (DT:[1476..1479] the) (NN:[1480..1488] increase)) (PP (IN:[1489..1491] in) (NP (NN:[1492..1497] serum) (NN:[1499..1508] estradiol) (NNS:[1509..1523] concentrations))))) (VP (VBN:[1524..1530] caused) (NP (-NONE-:[1530..1530] *)) (PP (IN:[1531..1533] by) (NP (NN:[1534..1544] cimetidine) (NN:[1545..1559] administration))))) (VP (MD:[1560..1563] may) (VP (VB:[1564..1568] help) (S (NP-SBJ (-NONE-:[1568..1568] *)) (VP (TO:[1569..1571] to) (VP (VB:[1572..1579] account) (PP-CLR (IN:[1581..1584] for) (NP (NP (NP (DT:[1585..1588] the) (NNS:[1589..1597] symptoms)) (PP (IN:[1598..1600] of) (NP (NN:[1601..1621] hyperestrogenization)))) (VP (VBN:[1622..1630] reported) (NP (-NONE-:[1630..1630] *)) (PP (IN:[1631..1633] in) (NP (NML (JJ:[1634..1638] long) (HYPH:[1638..1639] -) (NN:[1639..1643] term)) (NN:[1644..1654] cimetidine) (NN:[1656..1663] therapy))))))))))) (.:[1663..1664] .))) ;section 12 Span:1668..1712 ;PMID: 2638529 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1668..1672] PMID) (::[1672..1673] :) (CD:[1674..1681] 2638529) (NN:[1682..1683] -LSB-) (NNP:[1683..1689] PubMed) (::[1690..1691] -) (NN:[1692..1699] indexed) (IN:[1700..1703] for) (NNP:[1704..1712] MEDLINE-RSB-)))