闃挎垐缇庢媺姹€鐗囦汉浣撶敓鐗╃瓑鏁堟€х爺绌跺垎鏋
鍙戝竷鏃堕棿锛
2023-05-17
鏉ユ簮锛
涓€銆?/strong>鑳屾櫙
鎶戦儊鐥囨槸涓栫晫涓婃渶甯歌鐨勭簿绁為殰纰嶄箣涓€锛屾槸浠ュ績鎯呬綆钀斤紝鑷潃鍊惧悜涓轰富瑕佺壒寰佺殑甯歌鐨勬儏缁殰纰嶇患鍚堝緛銆備綔涓轰竴绉嶅鏉備笖缁忓父澶嶅彂鐨勭簿绁為殰纰嶏紝鎶戦儊鐥囩粰鎮ｈ€呫€佸搴拰绀句細甯︽潵浜嗗法澶х殑璐熸媴銆傚湪鍥藉唴澶栫殑鍙戠梾鐜囬€愭笎鍗囬珮锛屽挨鍏惰繘鍏?1涓栫邯涔嬪悗锛岀敓娲昏妭濂忕殑鍔犲揩瀵艰嚧绀句細鍘嬪姏澧炲ぇ锛屽畠鐨勫彂鐥呯巼瓒嬪娍鍛堟樉钁椾笂鍗囷紝璐┛鍦ㄥ悇涓勾榫勯樁娈碉紝浠ヤ骇鍚庣殑濡囧コ鎶戦儊鐥囨渶涓哄父瑙侊紝鑰屼笖瓒婃潵瓒婂亸鍚戜簬骞磋交鍖栵紝瀵硅繖绉嶇柧鐥呯殑閫傚綋绠＄悊瀵规暣涓ぞ浼氶兘鏄湁鐩婄殑銆傛姂閮佺棁鐨勬不鐤楅潪甯稿鏉傦紝鐮旂┒鍙戠幇瀹冪殑鍙戠梾鏈哄埗涓庢綔鍦ㄧ殑鐢熺墿瀛﹀紓甯告湁鍏炽€傜洰鍓嶆姉鎶戦儊鐨勪富瑕佽嵂鐗╂湁閫夋嫨鎬ф姂鍒?-HT閲嶆憚鍙栵紙SSRIs锛夈€佷笁鐜被銆佽お榛戠礌绫汇€佸宸磋兒锛圖A锛夋姂鍒跺墏浠ュ強鍘荤敳鑲句笂鑵虹礌锛圢E锛夐噸鎽勫彇鎶戝埗鍓傜瓑锛屼絾杩欎簺鑽墿鍓綔鐢ㄨ緝澶氫笖璁稿鎮ｈ€呭鐜版湁鐨勬姉鎶戦儊娌℃湁鍙嶅簲锛岄毦浠ョ紦瑙ｇ棁鐘躲€傚洜姝ゆ不鐤楁姂閮佺棁鐨勬柊鑽澏鐐规垨浣滅敤鏈哄埗鐨勫彂鐜板紩璧蜂簡浜轰滑鐨勫箍娉涘叧娉ㄣ€侟/span>
闃挎垐缇庢媺姹€鏄竴绉嶈お榛戠礌鍙椾綋婵€鍔ㄥ墏鍜?-HT2C鍙椾綋鎷姉鍓傘€侟/strong>鍔ㄧ墿鐮旂┒缁撴灉鏄剧ず锛岄樋鎴堢編鎷夋眬鑳芥牎姝ｆ樇澶滆妭寰嬬磰涔卞姩鐗╂ā鍨嬬殑鏄煎鑺傚緥锛屼娇鑺傚緥寰椾互閲嶅缓銆傞樋鎴堢編鎷夋眬鍦ㄥ绉嶆姂閮佺棁鍔ㄧ墿妯″瀷涓樉绀哄嚭鎶楁姂閮佷綔鐢ㄣ€傞樋鎴堢編鎷夋眬鑳界壒寮傛€у湴澧炲姞鍓嶉鐨川鍘荤敳鑲句笂鑵虹礌鍜屽宸磋兒鐨勯噴鏀撅紝缁嗚優澶栦簲缇熻壊鑳烘按骞虫湭瑙佹槑鏄惧奖鍝嶃€傚彈浣撶粨鍚堣瘯楠岀粨鏋滄樉绀猴紝闃挎垐缇庢媺姹€瀵瑰崟鑳哄啀鎽勬棤鏄庢樉褰卞搷锛屽α銆?beta;鑲句笂鑵虹礌鍙椾綋銆佺粍鑳哄彈浣撱€佽儐纰辫兘鍙椾綋銆佸宸磋兒鍙椾綋浠ュ強鑻簩姘崜绫诲彈浣撴棤鏄庢樉浜插拰鍔涖€備汉浣撶爺绌朵腑锛岄樋鎴堢編鎷夋眬瀵圭潯鐪犲叿鏈夋鍚戠殑鏃剁浉璋冩暣浣滅敤锛岃瀵肩潯鐪犳椂鐩告彁鍓嶏紝闄嶄綆浣撴俯锛屽紩鍙戠被瑜粦绱犱綔鐢ㄣ€侟/span>
闃挎垐缇庢媺姹€鐗囷紙鍟嗗搧鍚嶏細Valdoxan®锛堢淮搴︽柊锛?Thymanax®锛岃鏍?5mg锛夌敱娉曞浗鏂界淮闆呭叕鍙哥爺鍒讹紝浜?009骞磋幏寰楁娲茶嵂鍝佺鐞嗗眬鐨勬壒鍑嗗湪娆ф床涓婂競锛岀敤浜庢垚骞翠汉鎶戦儊鐥囩殑娌荤枟锛屼箣鍚庝簬2011骞达紝闃挎垐缇庢媺姹€閫氳繃鍘烠FDA鎵瑰噯鍦ㄤ腑鍥戒笂甯侟/strong>銆侟/span>
鏈枃缁撳悎鐩稿叧鎸囧鍘熷垯鍜屾枃鐚爺绌讹紝璇︾粏闃愯堪闃挎垐缇庢媺姹€鐗囦汉浣撶敓鐗╃瓑鏁堟€ц瘯楠岀殑涓€鑸€冭檻锛屽鏈搧浜轰綋鐢熺墿绛夋晥鎬х爺绌剁殑鑻ュ共鍏抽敭璁捐杩涜鎺㈣锛屾棬鍦ㄤ负姝ょ被浜у搧鐨勪豢鍒跺拰娉ㄥ唽鐢虫姤鎻愪緵鍙傝€冦€侟/span>
浜屻€?/strong>澶勬柟銆佺悊鍖栨€ц川涓庢憾鍑裹/strong>
1銆佸鏂瑰伐鑹裹/strong>
鏍规嵁Valdoxan®娆х洘鍏竷鐨勮鏄庝功[1]锛岄樋鎴堢編鎷夋眬鐗囧師鐮斿鏂逛俊鎭涓嬶細
2銆佺悊鍖栨€ц川
3銆佹憾鍑烘儏鍐袋/strong>
闃挎垐缇庢媺姹€鐗囧睘浜嶣CS I绫昏嵂鐗╋紝鍏跺湪浣撳唴婧跺嚭鍜屾笚閫忓潎涓嶄細闄愬埗鏈搧鐨勪汉浣撳惛鏀讹紝鏍规嵁鐩稿叧鏂囩尞鐮旂┒[3]瀵瑰師鐮斿埗鍓傛憾鍑虹殑鑰冨療锛岄樋鎴堢編鎷夋眬鐗囧湪鍚刾H浠嬭川涓殑婧惰В鎬у涓嬶細
涓夈€?/strong>鐢熺墿绛夋晥鎬ц瘎浠饵/strong>
闃挎垐缇庢媺姹€鐗囧彲鍚告敹杩涘叆琛€寰幆锛岀枟鏁堜笌琛€鑽祿搴﹀彲浠ュ缓绔嬭壇濂界殑鐩稿叧鎬э紝鏍规嵁銆婁互鑽姩瀛﹀弬鏁颁负缁堢偣璇勪环鎸囨爣鐨勫寲瀛﹁嵂鐗╀豢鍒惰嵂浜轰綋鐢熺墿绛夋晥鎬ц瘯楠屾寚瀵煎師鍒欍€嬶紝鏈搧搴斾互PK-BE鐨勬柟寮忚瘎浼板彈璇曞埗鍓備笌鍙傛瘮鍒跺墏鐨勭敓鐗╃瓑鏁堟€с€侲MA浜?018骞?鏈堥甯冧簡銆婇樋鎴堢編鎷夋眬鐢熺墿绛夋晥鎬х爺绌舵妧鏈釜鑽寚瀵煎師鍒欍€婞sup>[2]锛屽鏈搧鐢熺墿绛夋晥鎬х爺绌剁殑鍏抽敭璁捐鍋氬嚭浜嗙浉鍏虫帹鑽愩€侟/span>
1銆佺爺绌剁被鍨婞/strong>
EMA涓嵂鎸囧鍘熷垯鎺ㄨ崘浜嗙┖鑵圭粰鑽€佸崟鍓傞噺銆佷氦鍙変綋鍐呯爺绌讹紝鑰冭檻鍒版湰鍝佺敤娉曠敤閲忔帹鑽愮┖鑵瑰拰椁愬悗鏈嶇敤鍧囧彲锛屽洜姝ょ爺绌剁被鍨嬮€夋嫨鍚屾椂寮€灞曞崟娆＄粰鑽┖鑵瑰拰椁愬悗鐢熺墿绛夋晥鎬х爺绌舵洿绗﹀悎璇勪环鐩殑銆侟/span>
鏈搧鍙ｆ湇鍚庡惛鏀跺揩閫熶笖鑹ソ锛岀粷瀵圭敓鐗╁埄鐢ㄥ害浣庯紙鍙ｆ湇娌荤枟鍓傞噺<5%锛夛紝鏈夋槑鏄鹃杩囨晥搴旓紝涓綋闂村樊寮傝緝澶с€傚崟娆″彛鏈嶉樋鎴堢編鎷夋眬鐗囧悗锛岃嵂鍔ㄥ鍙傛暟Cmax鍜孉UC鐨勪釜浣撳唴鍙樺紓绯绘暟鍒嗗埆涓?3.34%~101.27%鍜?1.77%~65.87%[4]锛屾湁闈炲父鏄庢樉鐨勯珮鍙樺紓鑽墿鐨勭壒寰併€傜浉鍏虫枃鐚爺绌朵腑鍏剁┖鑵瑰拰椁愬悗Cmax鍜孉UC鐨勪釜浣撳唴鍙樺紓绯绘暟[5]濡備笅锛欬/span>
鍥犳锛屾湰鍝佺鐨勭敓鐗╃瓑鏁堟€х爺绌舵帹鑽愰噰鐢ㄩ儴鍒嗘垨閲嶅浜ゅ弶璁捐锛屽洜閲嶅浜ゅ弶璁捐鍙牴鎹弬姣斿埗鍓傜殑涓綋鍐呭彉寮傦紝灏嗙瓑鏁堟€у垽瀹氭爣鍑嗗湪80.00%~125.00%鐨勫熀纭€涓婇€傚綋鏀惧锛屾璁捐鏈夊埄浜庢纭瘎浼板埗鍓傚樊寮傦紝闄嶄綆鍒跺墏宸紓璇垽鐨勯闄┿€侟/span>
2銆佽鏍烽噰闆咟/strong>
闃挎垐缇庢媺姹€鍙ｆ湇鍚庡惛鏀跺揩閫熶笖鑹ソ锛屾湇鑽悗1-2灏忔椂鍐呰揪鍒拌娴嗗嘲娴撳害銆傝繘椋燂紙鏍囧噯楗鎴栭珮鑴傞ギ椋燂級涓嶅奖鍝嶉樋鎴堢編鎷夋眬鐨勭敓鐗╁埄鐢ㄥ害鎴栧惛鏀剁巼锛岄珮鑴傞ギ椋熶細澧炲姞涓綋宸紓銆傞樋鎴堢編鎷夋眬娑堥櫎閫熺巼蹇紝骞冲潎鐨勮娴嗘秷闄ゅ崐琛版湡涓?~2灏忔椂銆傚師鐮旇祫鏂欎互鍙婃枃鐚爺绌朵腑鑽唬鍔ㄥ姏瀛﹀弬鏁板涓嬶細
鏍规嵁涓婅堪PK鍙傛暟锛孊E鐮旂┒閲囪鐐硅璁℃椂闇€鍏虫敞杈惧嘲鏃堕棿鑼冨洿浠ュ強鍗婅“鏈燂紝绉戝鍦拌璁￠噰琛€鐐逛互婊¤冻鐢熺墿绛夋晥鎬х爺绌剁殑闇€瑕併€傛牴鎹師鐮旂浉鍏宠祫鏂欏拰鏂囩尞鏁版嵁锛岄樋鎴堢編鎷夋眬鐨凾max涓綅鍊奸泦涓湪0.68~2.0 h锛屽洜姝ゅ彲鍦ㄨ杈惧嘲鑼冨洿鍐呯瀛︾殑璁捐閲囪鐐癸紱闃挎垐缇庢媺姹€鍗婅“鏈熺殑鍧囧€艰寖鍥翠负0.960~1.58 h锛屽洜姝ら噰琛€缁堢偣璁捐涓?0 h鍗冲彲婊¤冻娉曡瀵逛簬閲囪缁堢偣涓嶇煭浜?涓湯绔秷闄ゅ崐琛版湡鐨勮姹傘€侟/span>
3銆佹娴嬬墿璐?/strong>
鏍规嵁銆婁互鑽姩瀛﹀弬鏁颁负缁堢偣璇勪环鎸囨爣鐨勫寲瀛﹁嵂鐗╀豢鍒惰嵂浜轰綋鐢熺墿绛夋晥鎬ц瘯楠屾寚瀵煎師鍒欍€嬶紝涓€鑸帹鑽愪粎娴嬪畾鍘熷舰鑽墿锛屽浜庝粠鍘熷舰鑽墿鐩存帴浠ｈ阿浜х敓鐨勪富瑕佷唬璋骇鐗╋紝褰撲唬璋骇鐗╀富瑕佷骇鐢熶簬杩涘叆浣撳惊鐜互鍓嶏紝骞朵笖浠ｈ阿浜х墿鏄捐憲褰卞搷鑽墿鐨勫畨鍏ㄦ€у拰鏈夋晥鎬ф椂锛屽簲娴嬪畾璇ヤ唬璋骇鐗┿€傚缓璁互鍘熷舰鑽墿璇勪环鐢熺墿绛夋晥鎬э紝浠ｈ阿浜х墿鐨勭浉鍏虫暟鎹敤浜庤繘涓€姝ユ敮鎸佷复搴婄枟鏁堢殑鍙瘮鎬с€侟/span>
闃挎垐缇庢媺姹€鍙ｆ湇鍚庝富瑕佺粡鑲濊剰CYP1A2鍚屽伐閰惰繀閫熶唬璋紝CYP2C9鍜孋YP2C19鍚屽伐閰朵篃鍙備笌闃挎垐缇庢媺姹€鐨勪唬璋紝浣嗕綔鐢ㄨ緝灏忋€備富瑕佷唬璋骇鐗╃緹鍖栭樋鎴堢編鎷夋眬鍜屽幓鐢插熀闃挎垐缇庢媺姹€鍧囨棤娲绘€т笖鍦ㄤ綋鍐呰繀閫熺粨鍚堬紝骞剁粡灏挎恫鎺掑嚭銆傚洜姝ゆ牴鎹硶瑙勶紝浠呴渶妫€娴嬭娴嗕腑鐨勫師褰㈣嵂鐗╅樋鎴堢編鎷夋眬鐨勬祿搴﹁繘琛岀敓鐗╃瓑鏁堟€х殑璇勪环銆侟/span>
4銆佺敓鐗╃瓑鏁堟€ц瘎浠饵/strong>
浠max銆丄UC0-t鍜孉UC0-∞浣滀负鏈搧绉嶇敓鐗╃瓑鏁堟€ц瘎浠风殑鎸囨爣锛屽浜庨€傜敤RSABE锛堝嵆鍙傛瘮鍒跺墏鐨勪釜浣撳唴鏍囧噯宸甋wr≥0.294锛夎瘎浠锋柟娉曠殑鐢熺墿绛夋晥鎬ц瘎浠锋寚鏍囷紝鍏剁殑鍗曚晶95%缃俊鍖洪棿涓婇檺搴斿皬浜庣瓑浜庨浂锛屽悓鏃跺彈璇曞埗鍓備笌鍙傛瘮鍒跺墏鐨勫嚑浣曞潎鍊兼瘮鐨勭偣浼拌鍊煎簲鍦?0.00%-125.00%鑼冨洿鍐呫€侟/span>
5銆佸浗鍐呯敵鎶ユ儏鍐袋/strong>
浠max銆丄UC0-t鍜孉UC0-∞浣滀负鏈搧绉嶇敓鐗╃瓑鏁堟€ц瘎浠风殑鎸囨爣锛屽彈璇曞埗鍓備笌鍙傛瘮鍒跺墏鐨凜max銆丄UC0-t鍜孉UC0-∞鐨勫嚑浣曞潎鍊兼瘮90%缃俊鍖洪棿搴斿湪80.00%-125.00%鑼冨洿鍐咃紙鍖呮嫭杈圭晫鍊硷級銆侟/span>
鐩墠鍥藉唴浠呬袱瀹朵紒涓氭嫢鏈夐樋鎴堢編鎷夋眬鐗囩敓浜ф壒鏂囷紝涓€鏄師鐮斾骇鍝佺淮搴︽柊锛屼簩鏄睙鑻忚豹妫嵂涓氱殑浜у搧闃跨編瀹併€傛睙鑻忚豹妫嵂涓氱殑闃挎垐缇庢媺姹€鏄洰鍓嶅浗鍐呭敮涓€鑾锋壒鍑嗛攢鍞殑闃挎垐缇庢媺姹€浠垮埗鑽紝浜?014骞磋幏鎵逛笂甯傦紝骞朵簬2022骞?8鏈?1鏃ュ浗鍐呴瀹堕€氳繃涓€鑷存€ц瘎浠枫€傜洰鍓嶅浗鍐呭竷灞€璇ュ搧绉嶅苟宸插紑灞旴E璇曢獙鐨勫寘鎷北涓滀含鍗埗鑽€佸寳浜鍏冨尰鑽€佹睙鑻忓畨蹇呯敓鍒惰嵂銆侀噸搴嗗崕妫埗鑽拰閲嶅簡鑽弸鍒惰嵂绛夊瀹朵紒涓氾紝鍏朵腑姹熻嫃瀹夊繀鐢熷埗鑽凡浜庝粖骞?鏈堜唤鑾峰緱CDE鐨勫彈鐞嗭紝杩欐槸鍥藉唴棣栧浠ユ柊娉ㄥ唽鍒嗙被鐢虫姤璇ュ搧绉嶇殑鑽紒锛屾湁鏈涙垚涓虹浜屽閫氳繃闃挎垐缇庢媺姹€鐗囦竴鑷存€ц瘎浠风殑浼佷笟锛屾墦鐮寸洰鍓嶅競鍦虹珵浜夋牸灞€銆侟/span>
缁煎悎鍒嗘瀽鐩墠璇ュ搧绉嶅湪CDE鐧昏鐨勪复搴婅瘯楠屼俊鎭紝鐢虫姤鐢熶骇鐨勪紒涓氱┖鑵瑰拰椁愬悗璇曢獙鍧囧熀鏈噰鐢ㄤ袱鍒跺墏銆佸洓鍛ㄦ湡鐨勫畬鍏ㄩ噸澶嶄氦鍙夎璁★紝鏍锋湰閲忎负68~136渚嬩笉绛夛紝鎻愮ず鏈搧BE璇曢獙鏍锋湰閲忎笌涓ゅ埗鍓傞棿璐ㄩ噺鐨勫樊寮傜浉鍏筹紝寮€灞曚綋鍐匓E鐮旂┒鍓嶅簲鍏呭垎璇勪及鍒跺墏闂寸殑宸紓锛屽彲閫氳繃棰勮瘯楠岃繘涓€姝ュ垽鏂埗鍓傝川閲忓苟鑾峰彇鍙傛瘮鍒跺墏涓綋鍐呭彉寮傛儏鍐碉紝涓烘寮忚瘯楠岀殑鏍锋湰閲忕‘瀹氭彁渚涗竴瀹氱殑鍙傝€冧緷鎹€侟/span>
鍥涖€?/strong>鎬荤粨
闃挎垐缇庢媺姹€鍙ｆ湇鍚庡惛鏀跺揩閫熶笖鑹ソ锛岀粷瀵圭敓鐗╁埄鐢ㄥ害浣庯紝涓綋闂村樊寮傝緝澶э紝杩涜浠垮埗鑽紑鍙戞椂闇€瑕佸厖鍒嗙悊瑙ｅ搧绉嶇殑浣撳唴杩囩▼锛屾纭爺鍒や綋鍐呭鐩稿叧鏉′欢涓嬪埗鍓傜殑宸紓锛屽苟閲囩敤绉戝鐨勮瘯楠岃璁★紝鍏虫敞褰卞搷涓綋鍐呭彉寮傜殑鍥犵礌锛岄噰鐢ㄥ噯纭殑鐢熺墿鏍锋湰娴嬪畾鏂规硶锛屾墠鑳芥洿濂姐€佹洿蹇湴鎺ㄨ繘鏈搧涓€鑷存€ц瘎浠风殑杩涚▼銆侟/span>
鏈枃鎬荤粨浜嗛樋鎴堢編鎷夋眬鐗囩敓鐗╃瓑鏁堟€х爺绌剁殑鐜扮姸锛屼互鏈熶负琛屼笟鎻愪緵鏈搧绉嶄复搴婅瘯楠岀瀛﹀拰涓撲笟鐨勮璁″弬鑰冦€傚湪楂樺彉寮傝嵂鐗╃殑BE鐮旂┒棰嗗煙锛屾垜鍙哥Н绱簡鎵庡疄鐨勭悊璁哄熀纭€鍜屼赴瀵岀殑椤圭洰缁忛獙锛屽叾涓紝姹熻嫃瀹夊繀鐢熷埗鑽殑闃挎垐缇庢媺姹€鐗囩殑BE璇曢獙鐢辨垜鍙稿畬鎴愶紝鎴戝徃鍙婁竴绔欏紡鏈嶅姟骞冲彴瀵瑰簲鐨勫瓙鍏徃鎵挎媴浜嗘湰椤圭洰鐨勫彈璇曡€呮嫑鍕熴€佷复搴婅瘯楠屻€佸垎鏋愭祴璇曘€佹暟鎹鐞嗕笌缁熻鍒嗘瀽绛夋湇鍔★紝閫氳繃涓€绔欏紡鏈嶅姟鐨勬瀬楂樻晥鐜囷紝瀹夊繀鐢熺殑闃挎垐缇庢媺姹€鐗囦汉浣撶敓鐗╃瓑鏁堟€х爺绌朵粎鐢ㄦ椂110澶╋紝鍦ㄧ爺绌剁粨鏉熷悗浠ラ潪甯搁珮鐨勬晥鐜囧畬鎴愪簡鐢虫姤璧勬枡鐨勬暣鐞嗭紝鑾峰緱浜嗙敵鍔炴柟鐨勯珮搴﹁鍙€侟/strong>
鍏€?/strong>鍙傝€冩枃鐚?/strong>
[1]闃挎垐缇庢媺姹€鐗囷紙Valdoxan®锛夎鏄庝功.
[2]European Medicines Agency. Agomelatine product-specific bioequivalence guidance. 2018.
[3]鑻楃嚂椋? 鎴堟枃鍏? 闄堝浗骞?绛? 闃挎垐缇庢媺姹€鐗囧湪4绉嶆憾鍑轰粙璐ㄤ腑鐨勪綋澶栨憾鍑虹爺绌禰J]. 涓浗鑽埧, 2013, 24(29):3.
[4]Pei Q, Wang Y, Hu Z-Y, Liu S-K, Tan H-Y, et al. (2014) Evaluation of the Highly Variable Agomelatine Pharmacokinetics in Chinese Healthy Subjects to Support Bioequivalence Study. PLoS ONE 9(10): e109300. doi:10.1371/journal.pone.0109300
[5]Agomelatin Sigillata 25 mg Filmtabletten, PAR.
[6]LC-MS_MS娉曟祴瀹氶樋鎴堢編鎷夋眬浜轰綋琛€娴嗕腑鐨勬祿搴﹀強涓ょ鐗囧墏鐨勭敓鐗╃瓑鏁堟€х爺绌迭/span>
[7]浜鸿娴嗕腑闃挎垐缇庢媺姹€娴撳害鐨勬祴瀹氬強鍏惰嵂浠ｅ姩鍔涘
[8] Li Meizhen,Tang Fang,Xie Feifan et al. Development and validation a LC-MSMS method for the simultaneous determination of agomelatine and its metabolites, 7-desmethyl-agomelatine and 3-hydroxy-agomelatine in human plasma Application to a bioequivalence study.[J] .J Chromatogr B Analyt Technol Biomed Life Sci, 2015, 1003 60-6.
棰勭煡鏇村鍝佺鍒嗘瀽锛岃鍜ㄨ↓↓↓
涓嬩竴椤
涓嬩竴椤