Influenza Report
 
Download pdf
 

 

 

   

²Ä¤Q³¹¡GÃĪ« - ¶ø´µ¥L°¶ (Oseltamivir)

Author(s) §@ªÌ:

Bernd Sebastian Kamps and Christian Hoffmann
Translator(s) ĶªÌ: ³¯¬¥§Ó Chan Lok Chi
Editor (Chinese Version)
½sªÌ(¤¤¤åª©¥»):
­³§®©yMary M.Y. Waye
  English version

 

 

 

[ back ]

²¤¶
(ºñ¦â³sµ²: §K¶O¥þ¤å¾\Äý)

¶ø´µ¥L°¶(Oseltamivir)¬O¤@ºØ¦³®Ä¤Î¦³¿ï¾Ü©ÊªºžJ¯À§í¨î¾¯¡A¯à°w¹ï§í¨î¬y¦æ·P«_¥Ò¯f¬r(influenza viruses A)¤Î¬y¦æ·P«_¤A¯f¬r(influenza viruses B)¤¤¯«¸gÓižJ(neuraminidase)ªº¬¡ÅD©Ê¡C¯«¸gÓižJ(neuraminidase)­t³d¤ÁÂ_­ì¯f¬r (virion)¤Wªº³è²G»Ä(sialic acid)©Î¨ä´Ý¾lª«¡A¨Ã¥B¨ó§U´²¼½¤ÎÂX´²¯f¬r­ì¡C·í¯f¬r­ì±µÄ²¨ì¶ø´µ¥L°¶(Oseltamivir)«á¡A¦¹ÃÄ·|¨Ï¨ì¯f¬r­ì»E¦X¦b±H¥D²Ó­M¤§ªí­±¡C³o¨ÇÃĪ«·|´î§C¯f¬r¦bÂH½¤¤Àªcª«¶Ç¼½ªº¯à¤O(McNicholl 2001)¡A±q¦Ó¹F¦Ü­°§C¯f¬r·P¬V¤O¡C

¶ø´µ¥L°¶(Oseltamivir)²{¦b¥D­n¥Î§@©ó¹w¨¾¬y¦æ·P«_¡A¤ÎªvÀø¤@¯ë²³æ«æ©Ê·P«_¼xª¬¡C©Ò¿×²³æ·P«_¼xª¬¬O«ü¤@·³¥H¤W±wªÌ¬V¯f®É¶¡¤£¨¬¤G¤Ñ¡CH5N1¯f¬r°ò¥»¹ï¶ø´µ¥L°¶(Oseltamivir)¤Q¤À±Ó·P¡A¦ý±q¥¼¦³¸ê®ÆÅã¥Ü¨ã¦³Á{§ÉªvÀø®Ä¯à¡C

Á{§É¬ã¨sÅã¥Ü¡A¦p¼xª¬¥X²{¤£¨¬48¤p®É¡AneuraminidasežJ§í¨î¾¯¯à¦³®Ä´î¤Ö·P«_¼xª¬¤§«ùÄò®É¶¡¡A¨Ò¦p¦Ù¦×»Äµh¡Bµo¼ö¤ÎÀYµh¥i´î¤Ö¬ù0.7-1¤é¡CÁ{§É®Ä¯à¥i¹F60-70%¡C¦pªG¹ï©ó¼xª¬¥X²{¤£¨¬30¤p®É¤§µo¼ö±wªÌ¡A¨äªvÀø§ó¬°¦³®Ä¡C¥t¥~¡A¦bªì¨B¹êÅç¶ø´µ¥L°¶(Oseltamivir)¦b²Ó­M¹ï¯f¬r·P¬Vªº§K¬Ì¤ÏÀ³¤¤¡A¤]¨S¦³¥X²{­t­±§@¥Î(Burger 2000)¡C

¥t¥~¡A¦³³ø§i«ü¶ø´µ¥L°¶(Oseltamivir)¥i¯à·|¤Þ­P»´·L­G¸z¹D¤£¾Aµ¥­t§@¥Î(Doucette 2001)¡C³Ìªñ¡A¶ø´µ¥L°¶(Oseltamivir)¥ç³Q²o¤Î»P´X©vºë¯«¥¢½Õ¤Î¨â¦W¤é¥»«C¦~¦Û±þ¡C¤£¹L¡A²{¦b¨S¦³ÃÒ¾Ú«üªA¥Î¶ø´µ¥L°¶(Oseltamivir)©M¦Û±þ¶É¦V¦³¦]ªGÃö«Y¡C

 

¤Æ¾Çµ²ºc

¶ø´µ¥L°¶(Oseltamivir)¬O¤A°òà­Ãþ«eÃÄ(prodrug)¡A¬O»Ý­n³z¹Là­¤ô¸Ñ§@¥ÎÂà¤Æ¦¨¬¡©Ê§Î¦¡¡A¶ø´µ¥L°¶(Oseltamivir)ßn°ò-4-¾LÓi-5-®ò°ò-3-(1-ethylpropoxy)-1-Àô¤AÖJ-1-ßn°òÁC»ÄÆQ (carboxylate[3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate.) ¡C¶ø´µ¥L°¶(Oseltamivir)ÃĪ«³]­pªºµo²{¬O§Q¥Îx¥ú¤ÀªRÃþ¦ü³è²G»Ä(sialic acid)»P¬y¦æ·P«_¥Ò¯f¬r¬¡©Ê°Ï¤ÎneuraminidasežJ¤§¶¡»E¦Xµ²´¹Åé±o¥X±Ò¥Ü (Lew 2000)¡C¶ø´µ¥L°¶(Oseltamivir)ªº»s¦¨¬O³z¹L§ïÅÜsialic acidÃþ¦üµ²ºc(¥]¬A¥[¤W¶Ýªo¯×Ãìlipophilic side chain)¡A¥Øªº¯à°÷¥Î©ó¤fªA(Kim 1998)¡C¦³Ãö¤§¤Æ¾Çµ²ºcµ{¦¡¦p¤U¡G

¦b³Ìªì®É´Á¡A¶ø´µ¥L°¶(Oseltamivir)¤Î¨ä¬¡©Ê¥NÁª«¡A³QºÙ¤§¬°GS4104¡BRo 64-0796¡BGS4071¤ÎRo 64-0802¡C

 

ÃĪ«¥NÁ°ʤO¾Ç

³z¹L¤fªA³~®|¡A¶ø´µ¥L°¶(Oseltamivir)«Ü§Ö·|³Q­G¸z¹D§l¦¬¡AµM«á¦b¨xŦÂà¤Æ¬°¬¡©Ê¶ø´µ¥L°¶(Oseltamivir)ßn°ò¥NÁª«¡A³Ì«á·|¤À§G¥þ¨­»ù¡A¥]¬A¤W¤Î¤U©I§l¹D(Doucette 2001)¡C¦pªG±q¤W­z³~®|¡A·í¤¤¬¡©Ê¶ø´µ¥L°¶(Oseltamivir)¥NÁª«ªº¥Íª«®Ä¯à©Ê¥i¹F80%¡C°ò¥»¤W¡A30¤ÀÄÁ¤º´N¥i·P¹î¦å²G¤¤ªº¶ø´µ¥L°¶(Oseltamivir)¥NÁª«¡A¦Ó¨ä³Ì°ª¿@«×¬O¤j¬ù3¦Ü4¤p®É¤§«á¡C±µþÓ¡A¨ä¥NÁª«¿@«×¥H¥b°I´Á6¦Ü10¤p®É¤@ª½°h´î(He 1999)¡C

³Ì²×¦å¼ß±Æ°h¥b°I´Á¡A¥H°·±d¦¨¤H¬°¨Ò¤j¬ù1.8¤p®É¡C¹ï©ó±w¦³µÇ·l®`¤§¯f¤H¨Ó»¡¡A¥NÁª«²M°£²v»P¦Ù»ÄÓþ(creatinine) ²M°£²v¬O¦¨¥¿¤ñ­°§C¡A§Y¬O¬ù¤fªAÃĪ««á23¤p®É¡A¦Ù®ò»ÄÓþ²M°£²v<30²@¤É/¤ÀÄÁ(Doucette 2001)¡C¬G¦¹¡AÀ³¹ªÀy¯f¤HªA¥Î¾¯¶q¡A´î¤Ö¦Ü79²@§J¨C¤é¤@¦¸¡A¹F¦Ü¦Ù®ò»ÄÓþ²M°£²v<30²@¤É/¤ÀÄÁ(1.8¤É/¤p®É)(He 1999)¡C

¼ß³J¥ÕÂH¦X¬°3%¡C³z¹LµÇ¤p²y¹LÂo¤Î¬¡©ÊºÞª¬¤Àªc¨â¤j§@¥Î¡A±NÃĪ«¤Î¨ä¬¡©Ê¥NÁª«±Æªn¥XÅé¥~¡A¦A¨S¦³Ä~«á·s³¯¥NÁ¶i¦æ¡C¤Æ¦Xª«¬J¨S¦³»P²Ó­M¦â¯ÀP450²V¦X¥\¯à®ñ¤Æ»Ã¯Àcytochrome P450 mixed-function oxidases©Îglucuronosyltransferases ²£¥Í¤ÏÀ³(He 1999)¡C¦]¦¹¡AÃĪ«»PÃĪ«¬Û¤¬§@¥Îªº¥i¯à¬O«Ü§C¡A¥ç´î§C¤F¹ïµÇ¤pºÞ¥~½¤²Ó­M­tÂ÷¤l¿é°e«¬±Æªnªºªý¹j¡C¥t¥~¡AProbenecidªý¹j¤FµÇŦ±Æªn¶ø´µ¥L°¶(Oseltamivir)ªº¯à¤O(Hill 2002)¡CÁöµM³oºØ±¡ªp¹ï¶ø´µ¥L°¶(Oseltamivir)Á{§ÉÀ³¥Î¤W¦³ÂI¤£§Q¡A¦ýProbenecid©Î¥i¼È¸Ñ¨M¶ø´µ¥L°¶(Oseltamivir)¦s¶qµu¯Ê°ÝÃD(Butler 2005)¡C

±w¦³¨x·l®`ªº¯f¤H¥¼¹ï©ó¶ø´µ¥L°¶(Oseltamivir)ªº¥NÁ¨èS¦³¦M¤Î¡A¤£»Ý­n½Õ¾ã¾¯¶q(Snell 2005)¡C

¹ï©ó¦~¦Ñ¤H¤h¤è­±¡A¬¡©Ê¥NÁª«¦bÅ餺ªº«ùÄò®É¶¡¤ñ¦~«C¤H°ª©ó25%¡C¦ý¤£»Ý­n½Õ¾ã¾¯¶q (He 1999)¡C

¥Ñ©ó¤j¬ù1¦Ü12·³¤pµ£¹ï¶ø´µ¥L°¶(Oseltamivir)¥NÁ²v¸û«C¦~©Î¦¨¤H¬°§Ö, ¦]¦¹ÃĪ«¦b¨äÅ餺ªº®É¶¡¸ûµu¡C¾¯¶q¤è­±¡A¤pµ£­n¼W¥[¦Ü2²@¤É/¤½¤ç2¤é¤@¦¸¡A¤~¬Ûµ¥©ó¦¨¤Hªº¥¿±`¾¯¶q(Oo 2001)¡C¤j¬ù1·³¥ª¥kÀ¦¨à¥ç¥i¥H¦³®Ä¦a¥NÁ¤αƪn¥X¶ø´µ¥L°¶(Oseltamivir)(Oo, 2003)¡C¦Ó¹ï©ó¸û¦~»´¨àµ£¨Ó»¡¡AªA¥Î¶ø´µ¥L°¶(Oseltamivir)®É¥i¯à¦³¨Ç¸T§Ò(¨£¬r©Ê)¡C

 

¬r©Ê

³Ì±`¨£ªº°Æ§@¥Î¬O»´·Läú¤ß¤Î¹Ã¦R¡A¦h¨£©óªAÃī᪺1-2¤Ñ¥X²{¡C

¥H¤W¤£¨}¤ÏÀ³§¡¬O¶ø´µ¥L°¶(Oseltamivir)±À¥X¥«­±«á©Ò±µÀò§ë¶D±o¨Ó¡C¥t¥~¡A¦b¨ä¥L§ë¶D¤¤¡A¥ç¤£ª¾¬O§_»PªA¥Î¶ø´µ¥L°¶(Oseltamivir)¦³Ãö¡C¦p¡G

  • ¥X¯l¡B­±³¡©Î¦Þ³¡¸~µÈ¡B¬r©Êªí¥ÖÃa¦º·»¸Ñ¯g(toxic epidermal necrolysis, TEN)
  • ¨xª¢¡B¨x¥\¯à¥X²{¤£¥¿±`
  • ¤ß«ß¤£»ô
  • ©âÝz¡B¯«§Ó¤£²M
  • ¥[³t¿}§¿¯f´c¤Æ

ªA¥Î¶ø´µ¥L°¶(Oseltamivir)À³¸Ó¤£·|¼W¥[¥X²{¥Ö½§¤ÏÀ³ªº¾÷·|(Nordstrom 2004)¡C¥t¥~¡A¦³¨Ç§{¶¡³ø§i«ü¥X¥i¯à¤Þ°_¯S²§©Ê¥Ö½§¤ÏÀ³¡AÁ|¨Ò¦³¤G¦ì¨xµw¤Æ¯f¤H¦Ó¶i¦æ¨xŦ¤Á°£¤â³N«á¡AªA¥Î§@¬°¹w¨¾ÃĶø´µ¥L°¶(Oseltamivir) ¤Î zanamivir¦Ó¥X²{¥þ¨­¬õ¯l(Kaji 2005)¡CŲ©ó¥H¤W¨Æ¥ó¡A­¹ª«¤ÎÃĪ«ºÞ²z§½(FDA)­n¨D¶ø´µ¥L°¶(Oseltamivir)²£«~¼ÐÅÒ¤W¥²©w¥[¤W¡u¥i¤Þ°_ÄY­«¥Ö½§/¹L±Ó¤ÏÀ³¡v¡C¦pªGªA¥ÎªÌ¸U¤@¥X²{ÄY­«¬õ¯l±¡ªp¡AÀ³¥ß¨è°±¤îªA¥Î©Î±µÄ²¦¹ÃÄ(FDA 2005)¡C

1·³¥H¤Uªº¨àµ£¤£«ØijªA¥Î¶ø´µ¥L°¶(Oseltamivir)¡A¦]¬°¶ø´µ¥L°¶(Oseltamivir)¹ï¥®¹«¶i¦æ¹êÅ礤¥X²{¹L¤¤¬r¤ÏÀ³¡C¥t¥~¡A¦pªG¾¯¶q¹F1000²@§J/¤½¤ç¶ø´µ¥L°¶(Oseltamivir)ÁC»ÄÆQ(¤j¬ù¬O¨àµ£«Øij¾¯¶q250­¿)¡A·|¥X²{¤j¶q¶ø´µ¥L°¶(Oseltamivir)ÁC»ÄÆQ¿n¦s©ó¤j¸£¡C¨Æ¹ê¤W¡A¨àµ£¹ï©ó¶ø´µ¥L°¶(Oseltamivir)ÁC»ÄÆQ¦b¸£¿n¦s¤§±¡ªp¬O¬ù¦¨¤H1500­¿¡C¦Ó¶ø´µ¥L°¶(Oseltamivir)¾¯¶q¹ï©óÀ¦¨àªº¼vÅT´N¨S¦³©úÅãÁ{§É¤ÀªR¡C±©®£¶ø´µ¥L°¶(Oseltamivir)¹ïÀ¦¨àªº¥¼¦¨¼ô¦å¸£«Ì»Ù(blood-brain barrier)¦³©Ò¼vÅT¡A¬G¤@¯ë³£¤£«ØijÅý1·³¥H¤U¨àµ£ªA¥Î¦¹ÃÄ¡C(¸É¥R:¤@¯ë1·³¨àµ£¦å¸£«Ì»Ù¤wÁͦ¨¼ô¡C)

¶ø´µ¥L°¶(Oseltamivir)ÄÝ¥¥°üºØÃþCÃĪ«¡A©Ò¥H¥i¯à¹ï¥¥°ü¤Î­L¨à¦³¤@©wªº¼vÅT¡C¦³¬ã¨sÅã¥Ü¡A¶ø´µ¥L°¶(Oseltamivir)¦¨¥÷¯à¥X²{©ó±Â¨Å¦Ñ¹«ªº¨Å²G¡A¦ý´N¨S¦³¦b¤HÅ餤°µ¹LÃþ¦ü¹êÅç¡A¬G¤£¯àªÖ©w¶ø´µ¥L°¶(Oseltamivir)¬O§_¯à±q¤HÃþªº¨Å²G¤¤±Æ¥X¡C

¹ï©ó¦³Ãö¯f¤HªA¥Î¶ø´µ¥L°¶(Oseltamivir)¦Ó¥X²{ºë¯«¥¢±`¤§³ø§i¡A¤é¥»·í§½¤w±N¯f¤H¥X²{ºë¯«²§±`¤ÏÀ³¬°ªA¥Î¶ø´µ¥L°¶(Oseltamivir)¤§°Æ§@¥Î¡C

 

¥\®Ä

ªvÀø

¶ø´µ¥L°¶(Oseltamivir)¤@¯ë¥Î¶q¬°75²@§J¨C¤Ñ2¦¸¡A¬°´Á5¤Ñ¡C¹ï©ó¦]¬y·P¦Óµo¿N¯f¤H¡Aµo¯f®É¶¡¤£¨¬1.5¤Ñªº¯f¤H¡A¥i´î¤Ö±w¯f®É¶¡ªº1.5¤Ñ¤Î´î»´ÄY­««×¬°38% (Treanor 2000)¡C¦pªG¯à¦bµo¯f12¤p®É¤º¡A§ó¦­±µ¨üÀøµ{¡A±w¯f®É¶¡§ó¥i´î¤Ö3¤Ñ¡CÁ`¤§¡A¶V¦­±µ¨ü¶ø´µ¥L°¶(Oseltamivir)¡A¶V§ó¯à´î¤Öµo¿N®É¶¡¤Î¼xª¬ÄY­«µ{«×©M«ì´_¥¿±`ªº®É¶¡ (Aoki 2003)¡C

¤@¯ëªø´Áµo¿N¯f¤H¡A¨äÅé?§¡°ª©ó39¢XC(Kawai 2005)¡C¶ø´µ¥L°¶(Oseltamivir)ÃĮĤj¬ùªA«á24¤p®É¤º²£¥Í(Nichson 2000)¡C±q¥]¬A10­Ó¦w¼¢¾¯¹ï¤ñÂùª¼¸ÕÅ礤ªº²Î¦X¤ÀªRmeta analysis¡Aµo²{Oseltamivir¥i´î§C±w¤U©I§l¹D¨Öµo¯g(Kaiser 2003)¡C

¹ï©ó±w¦³ºC©Ê©I§l¾¹©x¯e¯fªº±wªÌ¡A¥]¬AºC©Ê¤ä®ðºÞª¢¡Bªý¶ë©ÊªÍ®ð¸~¡B¤ä®ðºÞ­ý³Ý©Î¤ä®ðºÞÂX±i¡B¤ÎºC©Ê¤ßŦ¯fµ¥¶ø´µ¥L°¶(Oseltamivir)ªºªvÀø¥\®Ä¤Î¦w¥þ©Ê«h©|¥¼©ú½T¡C¦b¤@¨Ç¤p«¬ÀH¾÷´ú¸Õ¤¤¡A¶ø´µ¥L°¶(Oseltamivir)¥ç¦³©úÅã´î§C±w¨Öµo¯g¾÷·|(11% vs 45%)¡A¤Î¥Î§Ü¥Í¯Àªº»Ý­n(37% vs 69%) (³Æµù: «eªÌ¬°±µ¨üªvÀø²Õ¡F«áªÌ¬°¹ï¤ñ²Õ) (Lin 2006)¡C

¶ø´µ¥L°¶(Oseltamivir)ªvÀø¹ï¬y¦æ·P«_¤A¯f¬r(influenza viruses B)¤§®Ä¯à¤ñ¬y¦æ·P«_¥Ò¯f¬r(influenza viruses A)¬°§C¡C(¦³Ãö¹ïH5N1¯f¬rÃĮĬã¨s¨£¤U¤å)¡C

±q¸gÀپǨ¤«×¤W¡A¥]¬A¦Ò¼{¬y¦æ¯f¾Ç¸ê®Æ¤Î§Ü¯f¬rÃĪºÁ{§É¸ÕÅç¡Aµ²½×¬O¹ï©ó¤@¨ÇµL¬Ì­]ª`®g¤Î°ª¦M¬Ì­]ª`®g¯f¤H¶i¦æ¤ÀªR¡CÁ`½×¬O¨ú¥Î¶ø´µ¥L°¶(Oseltamivir)ªvÀø¬O¸û¬°²Å¦X¸gÀٮįq¡C¦Ó¨ä¥L¯f¤H¡A»Ýµ¥«Ý§Ö³t´ú¸Õµ²ªG¤~¶}©lªvÀø(Rothberg 2003)¡C

 

¹w¨¾

¦b¶i¦æ¶ø´µ¥L°¶(Oseltamivir)¹ï±wªÌ¤ÏÀ³´ú¸Õ¤¤¡A¶ø´µ¥L°¶(Oseltamivir)¤§¹w¨¾¤O¯à´î¤Ö±wªÌ¼Æ¥Ø[8/12 (67%)¦b¦w¼¢¾¯²Õ¤Î8/21(38%)¦b¶ø´µ¥L°¶(Oseltamivir)ªA¥Î²Õ]¡F¤Î´î¤Ö¤Þ°_·P¬V©Ê©I§l¹D¯e¯f(4/12 vs¡A0/21¡Fp=0.16¡F®Ä¯à61%)(Hayden 1999a)¡C³o¨Ç¼Æ¾Ú¬O±q1559°·±d¤ÎµL§K¬Ì¤ÏÀ³ªº¦¨¤H(18¦Ü65·³)¶i¦æ¤F¤»¬P´Á´ú¸Õ±o¥X¨Ó¡C¥L­Ì¤À¦¨¨â²Õ¡G¶ø´µ¥L°¶(Oseltamivir)ªA¥Î²Õ(75²@§J©Î150²@§J¨C¤é)¤Î¦w¼¢¾¯²Õ(Hayden 1999b)¡CªA¥Î¶ø´µ¥L°¶(Oseltamivir)(1. 2%)¤@²Õ¹ï±w¬y·P¾÷·|¤ñ°_ªA¥Î¦w¼¢¾¯¥t¤@²Õ¸û§C(4.8%)¡C¶ø´µ¥L°¶(Oseltamivir)ªº¹w¨¾¬y·P®ÄªG¹F74%(Hayden 1999b)¡C¥Î²Î¦X¤ÀªR¤èªk¤ÀªR¤CºØ¹w¨¾´ú¸Õ¤¤¡A¶ø´µ¥L°¶(Oseltamivir)¤§¹w¨¾¬y·P¯à¤O¹F70¦Ü90%(Cooper 2003)¡C

¹ï©ó¹w¨¾®a©~±µÄ²ªº¬y·P«ü¼Ð­Ó®×(IC)¡Aµo²{¶ø´µ¥L°¶(Oseltamivir)¯à¦³®Ä¹w¨¾¬y·P¹F89%(Welliver 2001)¡C¦b¤@­ÓÀH¾÷´ú¸Õ¤¤¡AªA¥Î¦w¼¢¾¯²Õ¦³12.6%(26/206)¥X²{¬y·P¼xª¬¡A¬Û¤ÏªA¥Î¶ø´µ¥L°¶(Oseltamivir)²Õ¥u¦³1.4%(3/209)¡C¦b¥t¤@ÀH¾÷´ú¸Õ¤¤¡A®a©~±µÄ²¤H¦b¦³¬y·P«ü¼Ð­Ó®×¡A§Y¥X²{Ãþ¦ü¬y·P¼xª¬(¦pÅé·Å°ª¹L37.8¢XC¤Î«y¹Â)®É«hÀH¾÷¤À¦¨¨â²Õ¡G¤@²ÕÅý¨ä¶i¦æ¤Q¤Ñªº±µÄ²¯f¬r«á¹w¨¾ªvÀø(post-exposure prophylaxis¡APEP)¥t¤@²Õ«hµo¯f«á¤~ªvÀø¡C©Ò¦³«ü¼Ð­Ó®×«h±µ¨ü¤­¤ÑªvÀø(Hayden 2004)¡A¶ø´µ¥L°¶(Oseltamivir)¹w¨¾ªvÀøPEP¯à¦³68%¹w¨¾²v¡C³æ³æ¹ï¤ñªvÀøªº«ü¼Ð­Ó®×¡AªA¥Î¦w¼¢¾¯²Õ¦³13%(33/258)¥X²{¬y·P¼xª¬¡A¬Û¤ÏªA¥Î¶ø´µ¥L°¶(Oseltamivir)²Õ¥u¦³4%(10/244) (p=0017)¡C

±q¸gÀپǨ¤«×¤W¡AªA¥Î¶ø´µ¥L°¶(Oseltamivir)¹w¨¾¬y·P¤ñ°_ªA¥Îamantadine©Î¤£§@¥ô¦ó¹w¨¾§ó²Å¦X¸gÀٮįq(Risebrough 2005)¡C¦ý¬O¥t¥~¤@­Óªñ´Áªº²Î¦X¤ÀªR¡A»{¬°¶ø´µ¥L°¶(Oseltamivir)¹ï©ó¸ûÄY­«ªº¶Ç¬V©Ê©Î¬y¦æ©Êªº·P«_¯f¸û¦³©úÅã¥\®Ä¡A¦ý¹ï©ó±±¨î©u¸`©Ê·P«_¯f´N¤£¤Ó©úÅã(Jefferson 2006)¡C

 

¿ï¾Ü©Ê¯f¤H²Õ¸s

³z¹LÂùª¼¤Î¦w¼¢¾¯¤èªk¡A¹ï548µê®z¤Î¦~¦Ñªº¦b®a¤H¤h(¤¤¦ì¼Æ¬°81·³¡A¦h©ó80%¨ü§K¬Ìª`®g)¶i¦æ¤fªA¶ø´µ¥L°¶(Oseltamivir)¹w¨¾¬y·P¹êÅç(Peters 2001)¡C¹ï¤ñªA¥Î¦w¼¢¾¯¡A¶ø´µ¥L°¶(Oseltamivir)¯à´î§C92%¤H¤h±w¬y·P¾÷·|(1/276 = 0.4 % ¡F12/272 = 4.4 %)¡C¦Ó¥B¶ø´µ¥L°¶(Oseltamivir)¯à¦³®Ä¦a´î§C±w¬y·PÄ~«á¨Öµo¯g(Peters 2001)¡C

¨àµ£¡G¨à¬ì¯f¤H¤fªA¶ø´µ¥L°¶(Oseltamivir)«á¡A¯à´î¤Ö±w¬y·P®É¶¡¦Ü36¤p®É¤Î¨ä¥L¥X²{¼xª¬®É¶¡(¦p«y¹Â¡Bµo¿Nµ¥)¡C¥[¤W¡A¥ç´î¤Öªº44%±w¤¤¦Õª¢¾÷·|¤ÎªA¥Î§Ü¥Í¾¯ªº¦¸¼Æ (Whitley 2001)¡C¦b³Ìªñ¬ã¨s¤¤¡Aµo²{¶ø´µ¥L°¶(Oseltamivir)¯àÁYµu­ý³Ý¨àµ£¥X²{¼xª¬®É¶¡¡B§ïµ½¨äªÍ¥\¯à¥H¤Î´î§C­ý³Ý´c¤Æ¾÷·|(51 % ¹ï 68 %) (Johnston 2005)¡C

¦Ü©ó¡A¶ø´µ¥L°¶(Oseltamivir)¹ï©óºC©Ê¤ßŦ¯e¯f¤Î©I§l¹D¯e¯fªº¥\®Ä¤´¥¼½T©w¡C¥t¥~¡AµL¸ê®ÆÅã¥Ü¡A¦]¶i¦æ¶ø´µ¥L°¶(Oseltamivir)ªvÀø¦Ó¥X²{ÄY­«±¡ªp¡A»Ý°e°|¦¬®e¡CÁÙ¦³¡A¯f¤H°µ¹L°©Åè²¾´Ó¤â³N­º¤»­Ó¤ë«á¡A¦]¬Ì­]ªº§K¬Ì¤O¤Ó§C¦Ó±Ä¥Î¶ø´µ¥L°¶(Oseltamivir)§@¥Î¹w¨¾¤§¥Î(Machado 2004)¡C

 

¹ïH5N1¸V¬y·P¤§®Ä¯à

¦b¸ÕºÞ¹êÅ礤¡A¶ø´µ¥L°¶(Oseltamivir)ªº½T¹ï¬y¦æ·P«_¥Ò¤Î¤A¯f¬r(influenza viruses A & B)¦³¤@©wªº§Ü¯f¬r¯à¤O¡A¥]¬A´¿¤@«×¦b­»´ä¸v­hªºH5N1 ¤Î H9N2¯f¬r(Leneva 2000)¡C®Ú¾ÚWTO¸ê®Æ©Ò±o¡AH5N1¸V¬y·P­Ó®×¤w´î¤Ö(Writing Committee of the WHO 2005)¡C¬Û¤Ï¡A¤´¥¼¦³¹ê½èÅã¥Ü¶ø´µ¥L°¶(Oseltamivir)¯à¦³®Ä´î¤ÖH5N1¯f¬r·P¬V¡C³Ìªñ¡A§ó¦³³ø§i«ü¥X§Y¨Ï¾A·í¾¯¶q¡A¤]¤£¯à§í¨î¯f¬r¦Û§Ú½Æ»s¡A¬Æ¦Ü¤Þ°_§ÜÃĤÏÀ³(de Jong 2005)¡C¹ï©ó¦¹°ÝÃD¡A¬O§_À³¥[­«¾¯¶q©Î©µªøªvÀø®É¶¡¤´¦bª§½×¤¤¡C¥t¤@­Ó°Q½×°ÝÃD¡A¶ø´µ¥L°¶(Oseltamivir)¯à¾A¥Î©ó«á´Á¯f¬r¤w¶i¦æ½Æ»s³o­Ó±¡ªp¡C²{¥u±o¨Ç·¥¦³­­ÃÒ¾Ú»¡©ú«á´Á±Ä¥Î¶ø´µ¥L°¶(Oseltamivir)¯à´î¤Ö¯f¬r¦bÅ餺¼Æ¶q¡A¥H¤Î¼W¥[¯f¤H¦s¬¡²v(de Jong 2005)¡C³o­Ó¼Æ¾Úµ²ªG¡A»P¦³Ãö¦Ñ¹«¹êÅç¬O¤@­Pªº¡C¨Ò¦p¶i¦æ5¤ÑÀøµ{ªº¸Ü¡A¹êÅç¦Ñ¹«ªº¦s¬¡²v¹F50%¡F¶i¦æ8¤ÑÀøµ{ªº¸Ü¡A¹êÅç¦Ñ¹«ªº¦s¬¡²v¹F80% (Yen 2005b)¡C¥t¥~¤@­Ó¹êÅç¡A§Y¨Ï©µ¿ð¤F5¤Ñ¶i¦æÀøµ{¡A¨ä¦s¬¡²v¤]¥i¥Ñ0%¤É¦Ü75% (McCullers 2004)¡C

¸û°ª¶ø´µ¥L°¶(Oseltamivir)¾¯¶q¤]ºâ¹ï¤HÅé¦w¥þ¡C¸ê®ÆÅã¥Ü¡A5¤ÑÀøµ{150²@§J¨C¤Ñ¤G¦¸©Î6©PÀøµ{75²@§J¨C¤Ñ¤G¦¸§@¹w¨¾¤§¥Î¡A¤]¥iºâ¬O³\¥i¤§¾¯¶q(Ward 2005)¡C

 

¹ï1918¦~¬y¦æ·P«_¯f¬r¤§®Ä¯à

³oºØµ²¦X©Ê¯f¬r¬O¥Ñ1918 NA©Î1918 HA¤Î1918 NA¨â­Ó¤èªkºc¦¨¡C¦Ó¶ø´µ¥L°¶(Oseltamivir)¥¿¥¿¯à§í¨î¦³Ãö¦b²Ó­M²Õ´°ö¾i¹êÅç©Î¦Ñ¹«¤¤ªºµ²¦X©Ê¯f¬r¡C¦]¦¹¡A»{¬°¶ø´µ¥L°¶(Oseltamivir)¯à§í¨î1918¦~¬y¦æªº·P«_¯f¬r©Î¨äÃþ¦üªº¯f¬r(Tumpey 2002)¡C

 

©è§Ü©Ê

¦b¸ÕºÞ¹êÅ礤¡ANA¬ðÅÜE119V, R292K, H274Y, and R152K·|¤Þ°_¹ï¶ø´µ¥L°¶(Oseltamivir)§ÜÃÄ©Ê(McKimm-Breschkin 2003)¡C¦Ó¯f¬r¦³R292K¬ðÅܪº¸Ü¡A¨ä¦Û§Ú½Æ»s¯à¤O·|³à¥¢¡A¤Î¨ä­P¯f¯à¤O¦b¹êÅç¦Ñ¹«¤¤¤ñ³¥¥Í«¬§C©ó10,000­¿(Tai 1998)¡C¦P¼Ë¦Ó¨¥¡A·í¦³H274Y¬ðÅܪº¸Ü¡A¨ä¦Û§Ú½Æ»s¯à¤O·|´î¦Ü3«×(logs) (Ives 2002)¡A¬G»Ý¦h©ó100­¿¯f¬r¼Æ¶q¤~¥i¨Ï¥ÕÃ^­P¯f¡A¤ñ³¥¥Í«¬¶Ç¼½¤O§C(Herlocher 2004)¡C

®Ú¾Ú¥H¤W©ÒÁ¿¡A¯f¬r¥X²{¬ðÅܦӼvÅT¥¦¾AÀ³¯à¤Oªº¸Ü¡A®Ú¥»¤£»Ý­nÃöª`¡C³Ìªñ¡A¦³¨Ç³ø§i½èºÃH5N1¯f¬r¯à¤Þ°_¹ï¶ø´µ¥L°¶(Oseltamivir)°ª«×§ÜÃĩʳoºØÁ¿ªk(Le 2005, de Jong 2005)¡CÁöµM§Y¨ÏªA¥Î¾A·í¶ø´µ¥L°¶(Oseltamivir)¾¯¶q(¦³¯f¼x¤§«á¤@¤ÑªA¥Î)¡A¥¼¯à§í¨î¯f¬r¦Û§Ú½Æ»s¤Î¤Þ°_§ÜÃĪº¯f¬r¡A¦ý«ÜÃøª¾¹D¯u¥¿­ì¦]¬O§_¥Ñ©ó¾É­P¯f¬r¤j¶q½Æ»s©Î­«¯g¯f¤HÅ餺ªºÃIJz¤ÏÀ³¤w¦³§ïÅÜ¡C

¤Ï¤§¡A©u¸`©ÊH1N1¤ÎH3N2¬y·P¯f¬r¦b¦¨¤H¤Î¦~«C¤H¤¤²£¥Í¹ï§Ü¦]¤l¯à¤O¸û§C¡A¦h¨£©ó¨àµ£¡C¨ä¤@¦³¬ã¨s«ü¥X¡A¯f¬r¤¤¯«¸gÓižJ(neuraminidase)¬ðÅܬ°9/50¯f¤H(18%)(Kiso 2004) ¡C¦Ó¦]¬°¨àµ£¬O¨ä¯f¬r¨ä¤¤¤@­Ó¶Ç¼½´C¤¶¡A§Y¨Ï¤­¤Ñ«á±µ¨üªvÀø¡A³o¨Ç¸ê®Æ¤]»Ý½Õ¬d¡C

¦b¹êÅç¬ã¨s¤¤¡A¥iµo²{§Ü¶ø´µ¥L°¶(Oseltamivir)¬ðÅܲ§ºØ¤Î§ÜZanamivir¬ðÅܲ§ºØ·|µo¥Í¥æ¤e©è§Ü©Ê(Cross-resistance)¡C¨ä¤¤¨â­Ó¨ü¶ø´µ¥L°¶(Oseltamivir)¤Þ°_¬ðÅÜ(E119V, H274Y and R292K)·|¦b¯«¸gÓižJ(neuraminidase)¦P¤@­ÓÓi°ò»Ä¾lª«¡A¥X²{©ó¨ä¤¤¨â­Ó¨üZanamivir¤Þ°_¬ðÅܪº¯f¬r¤º(E119G/A/D, R152K and R292K) (Tamiflu 2005)¡C

 

ÃĪ«¬Û¤¬§@¥Î

®Ú¾ÚÃIJz¾Ç¤ÎÃĪ«°Ê¤O¾Ç¬ã¨sÅã¥Ü¡AÃĪ«ªvÀø¤W¥X²{¶ø´µ¥L°¶(Oseltamivir)»P¨S¦³¶ø´µ¥L°¶(Oseltamivir)¬Û¤¬§@¥Î (Tamiflu 2005)¡C±N¶ø´µ¥L°¶(Oseltamivir)(©Î¶ø´µ¥L°¶(Oseltamivir)ßn°ò)¨Ã¤£¬O¤Î²Ó­M¦â¯ÀP450ªº°ò½è©Î§í¨î¾¯¡C

 

¥Îªk«Øij

¼Ú·ù

¶ø´µ¥L°¶(Oseltamivir)(¯S±ÓºÖTamiflu?)¤w¨ü¼Ú·ù¤¤¥¡³\¥i¡C¥Îªk»¡©ú¤Î¾¯¶q§¡®Ú¾Ú¬ü°ê¥«³õ»{¥i¡C

¬ü°ê

¶ø´µ¥L°¶(Oseltamivir)¥Î§@ªvÀø¤@¯ë²³æ«æ©Ê·P«_¼xª¬¡C©Ò¿×²³æ·P«_¼xª¬¬O«ü¤@·³¥H¤W±wªÌ¥X²{¼xª¬¯f®É¶¡¤£¨¬¤G¤Ñ¡C¦AªÌ¡A¶ø´µ¥L°¶(Oseltamivir),¾A¥Î©ó¤@·³¥H¤W±wªÌ¹w¨¾¬y·P¡C

¤@¯ë«ü©wªvÀø¾¯¶q¡A13·³©Î¥H¤W¤H¤h¬°75²@§J¨C¤Ñ¤G¦¸¡A¥H5¤Ñ¤@­ÓÀøµ{¡C¦p¤£¯à§]ªA½¦Ån¤§¨àµ£©Î¦¨¤H¡A¥i¿ï¾Ü30¡B45¤Î60²@§J¤fªAÃIJG¨C¤Ñ¤G¦¸¡C «Øij¾¯¶q¡G

Åé­«
5¤Ñ«Øij¾¯¶q
≤15 ¤½¤ç(≤ 33 ½S)
30²@§J¨C¤Ñ¤G¦¸
> 15¤½¤çto 23¤½¤ç(> 33 ½S¦Ü 51 ½S)
45²@§J¨C¤Ñ¤G¦¸
> 23 ¤½¤çto 40 ¤½¤ç(> 51 ½S¦Ü 88 ½S)
60²@§J¨C¤Ñ¤G¦¸
> 40 ¤½¤ç (> 88 ½S)
75²@§J¨C¤Ñ¤G¦¸

8·³¥H¤W¨àµ£¦p¯à§]ªAÃĪ«¥i¥Î75²@§J½¦Ån°t¤è¡C

¹w¨¾¤è­±¡A¤@¯ë«Øij¾¯¶q75²@§J¨C¤é¤@¤Ñ¡A¬°´Á¦Ü¤Ö¤C¤é¡C¹ï©ó¤@·³©Î¥H¤W¨à¬ì¯f¤H¤§¤fªA¶ø´µ¥L°¶(Oseltamivir)¾¯¶q¬°¦p¤U¡G

Åé­«
7¤Ñ«Øij¾¯¶q
≤15 ¤½¤ç(≤ 33 ½S)
30²@§J¨C¤Ñ¤G¦¸
> 15¤½¤çto 23¤½¤ç(> 33 ½S¦Ü 51 ½S)
45²@§J¨C¤Ñ¤G¦¸
> 23 ¤½¤çto 40 ¤½¤ç(> 51 ½S¦Ü 88 ½S)
60²@§J¨C¤Ñ¤G¦¸
> 40 ¤½¤ç (> 88 ½S)
75²@§J¨C¤Ñ¤G¦¸

 

Á`µ²

¶ø´µ¥L°¶(Oseltamivir)¬O¤@ºØ,¨ã¿ï¾Ü©Ê¯«¸gÓižJ§í¨î¾¯(neuraminidase inhibitor)¡C±µ¨üªvÀø®É¶¡¤@©w­n¦b¥X²{¼xª¬«á48¤p®É¤º¡A¦ý³Ì¦n·íµM¬O¾¨§Ö©Î¦b24¤p®É¤º¡C¤@¯ë¤H¹ï¶ø´µ¥L°¶(Oseltamivir)¦³­@ÃĤO¡C

°ê®a·í§½«Øij¤£À³±N¶ø´µ¥L°¶(Oseltamivir)´À¥N¬°¦­´Á¬Ì­]¡C

¹ï©óH5N1¯f¬r¡A¶ø´µ¥L°¶(Oseltamivir)¤§¥\®Ä¡B³Ì¨Î¾¯¶q¤Î¥ÎÃÄÀøµ{¤´¦³«ÝªÖ©w¡C

 

°Ó«~¦WºÙ¡GTamiflu™

75²@§J½¦Ån (10²É¤@±Æ) ¤fªA¯»¾¯ (¥Î¤ô½Õ¨î12²@§J/²@¤É¡F¤@¯ë¤ô¾ê§t25²@¤ÉÄa¯B²G)¡C

ÃĪ«ºØÃþ¡G¯«¸gÓižJ§í¨î¾¯(neuraminidase inhibitor)

ªA¥Î«ü¤Þ¡G¾A¥Î©ó¤@¯ë«D½ÆÂø©Ê«æ©Ê¬y·P±wªÌ(1·³¥H¤W)¡A¥X²{¼xª¬¤£¨¬¨â¤Ñ¡C ¥Î§@¹w¨¾¬y·P¡A¤@¯ë¾A¥Î©ó1·³¥H¤W¤§±wªÌ¡C

¼Ð·Ç¾¯¶q(¥Î§@ªvÀø)¡G75²@§J¨C¤é¨â¦¸¡A¬°´Á¤­¤Ñ¡C ¨à¬ì±wªÌ©Î§]ªA»Ùꤧ¦¨¤H±wªÌ¡A¥i¿ï¥Î¤fªA²G¾¯¡C¾¯¶q«Øij½Ð°Ñ¦Ò¥H¤W¡C

¼Ð·Ç¾¯¶q(¥Î§@¹w¨¾)¡G75²@§J¨C¤é¤@¦¸¡A¬°´Á¦Ü¤Ö¤C¤Ñ¡C ¨à¬ì±wªÌ©Î§]ªA»Ùꤧ¦¨¤H±wªÌ¡A¥i¿ï¥Î¤fªA²G¾¯¡C¾¯¶q«Øij½Ð°Ñ¦Ò¥H¤W¡C

¯S®í¾¯¶q¡G·í±wªÌ¨ä¦å²M¦Ù»ÄÓþ²M°£²v(serum creatinine clearance)¤@ª½¤¶¥G10-30²@¤É/¤ÀÄÁ«hªA¥ÎªvÀø¾¯¶q¬°75²@§J¨C¤é¨â¦¸¡A¬°´Á¤­¤Ñ¡B¹w¨¾¾¯¶q¬°75²@§J¹j¤Ñ©Î30²@§J¨C¤Ñ¡C¤w¤£¯à¾A¥Î©ó¶i¦æ±`³W¦å²G³zªR©Î¸¡½¤³zªR¤§¥½´ÁµÇ¯f±wªÌ«h¥¼¦³©ú½Tªº¾¯¶q¥i«Øij¡C

ÃĪ«°Ê¤O¾Ç¡G¤fªA¶ø´µ¥L°¶(Oseltamivir)¤@¯ë¦b­G¸z¹D§l¦¬¡AµM«áÂà¤Æ¦¨¶ø´µ¥L°¶(Oseltamivir)ßn°ò(carboxylate)¡C³Ì«á¡A¶ø´µ¥L°¶(Oseltamivir)ßn°ò³z¹L§¿²G±Æ¥XÅé¥~¡A¤@¯ë¥b°I´Á(half-life)¬°6-10¤p®É¡C

¸T§Ò¡G¶ø´µ¥L°¶(Oseltamivir)¤£¾A¥Î©ó1·³¥H¤U¤§¬y·P±wªÌ¡C°£«D¦¹ÃĹ便°üªº§Q¯q¦X²z¦a°ª©ó¥i¯à¦M®`­L¨àªº­·ÀI§_«h¤£¾A¥Î(ÄÝ¥¥°üºØÃþCÃĪ«)¡C

ÃĪ«¬Û¤¬§@¥Î¡G¥¼¦³©úÅ㪺ÃĪ«¬Û¤¬§@¥Î¡C

°Æ§@¥Î¡G¤@¯ë°Æ§@¥Î·Å©M©Î¤¤«×ªº¡A¦p´c¤ß¤Î¹Ã¦R¡A¦h¨£©óªAÃÄ­º¨â¤Ñ¡C

¥mÅñ¡G·í¥X²{¬y·P¼xª¬«á¡A±wªÌÀ³ºÉ¦­ªA¥ÎÃĪ«¡C¦P¼ËÀ³¦b±µÄ²¯f¬r¦ý¥¼·P¬V«e¡AªA¥ÎÃĪ«§@¹w¨¾¡C

¤p¦Y«áªAÃÄ¥i´î»´µu¼È©Ê¸z¹D¯¿¶Ã¡C

¹ï¦Ñ¦~±wªÌ¤£»Ý½Õ¾ã¾¯¶q¡C

¦P¤@®É¶¡¶i­¹¤ÎªAÃÄ¡A¤£·|¹ïÃĪ«¦b¦å¤¤³Ì°ª¿@«×¤ÎAUC¦³¼vÅT¡C

ÃĪ«¶J¦s©ó³±²D¦a¤è(¬ù25¢XC©Î77¢X F)¡Aµu¼È¶J©ñ¥ç¥i©ó15¢X to 30¢X C (59¢X to 86¢X F)¡C

¶ø´µ¥L°¶(Oseltamivir)¤fªA²G¾¯¡A³Ì¦n¥ÑÃľ¯®v½Õ¨î«á°tµoµ¹¯f¤H¡C

¶J¦s¤fªA²G¾¯¡A·Å«×¬ù2¢X to 8¢X C (36¢X to 46¢X F)¡A¤£¥i¦BÂáC

¶ø´µ¥L°¶(Oseltamivir)¤£¥i¥N´À¬y·P¬Ì­]¡A±wªÌÀ³¸òÀH°ê®a·í§½«ü¤Þ±µ¨ü¨C¦~¬y·P¬Ì­]¡C

 

¤¬Ápºô¸ê®Æ

¼Ú¬w: http://influenzareport.com/link.php?id=14

¬ü°ê: http://influenzareport.com/link.php?id=1

 

°Ñ¦Ò

  1. Aoki FY, Macleod MD, Paggiaro P, et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 2003; 51: 123-9. Abstract: http://amedeo.com/lit.php?id=12493796 - Full text at http://jac.oxfordjournals.org/cgi/content/full/51/1/123
  2. Burger RA, Billingsley JL, Huffman JH, Bailey KW, Kim CU, Sidwell RW. Immunological effects of the orally administered neuraminidase inhibitor oseltamivir in influenza virus-infected and uninfected mice. Immunopharmacology 2000; 47: 45-52. Abstract: http://amedeo.com/lit.php?id=10708809
  3. Butler D. Wartime tactic doubles power of scarce bird-flu drug. Nature 2005; 438: 6.
  4. Calfee DP, Hayden FG. New approaches to influenza chemotherapy. Neuraminidase inhibitors. Drugs 1998; 56: 537-53. Abstract: http://amedeo.com/lit.php?id=9806102
  5. Carr J, Ives J, Kelly L, et al. Influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir carboxylate has altered properties in vitro and is compromised for infectivity and replicative ability in vivo. Antiviral Res 2002; 54: 79-88. Abstract: http://amedeo.com/lit.php?id=12062393
  6. Centers for Disease Control. Neuraminidase inhibitors for treatment of influenza A and B infections. MMWR Recomm Rep 1999; 48: 1-9. Abstract: http://amedeo.com/lit.php?id=10632443 - Full text at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4814a1.htm
  7. Chokephaibulkit K, Uiprasertkul M, Puthavathana P, et al. A child with avian influenza A (H5N1) infection. Pediatr Infect Dis J 2005; 24: 162-6. Abstract: http://amedeo.com/lit.php?id=15702046
  8. Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG. Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. BMJ 2003; 326: 1235. Abstract: http://amedeo.com/lit.php?id=12791735 - Full text at http://bmj.bmjjournals.com/cgi/content/full/326/7401/1235
  9. de Jong MD, Tran TT, Truong HK, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 2005; 353: 2667-72. Abstract: http://amedeo.com/lit.php?id=16371632 - Full text at http://content.nejm.org/cgi/content/full/353/25/2667
  10. Doucette KE, Aoki FY. Oseltamivir: a clinical and pharmacological perspective. Expert Opin Pharmacother 2001; 2: 1671-83. Abstract: http://amedeo.com/lit.php?id=11825310
  11. Dreitlein WB, Maratos J, Brocavich J. Zanamivir and oseltamivir: two new options for the treatment and prevention of influenza. Clin Ther 2001; 23: 327-55. Abstract: http://amedeo.com/lit.php?id=11318072
  12. Dutkowski R, Thakrar B, Froehlich E, Suter P, Oo C, Ward P. Safety and pharmacology of oseltamivir in clinical use. Drug Saf 2003; 26: 787-801. Abstract: http://amedeo.com/lit.php?id=12908848
  13. FDA - Food & Drug Administration. FDA Approves Tamiflu for Prevention of Influenza in Children Under Age 12. Accessed on 8 January 2006 from http://www.fda.gov/bbs/topics/news/2005/NEW01285.html
  14. Gubareva LV, Kaiser L, Hayden FG. Influenza virus neuraminidase inhibitors. Lancet 2000; 355: 827-35. Abstract: http://amedeo.com/lit.php?id=10711940
  15. Gubareva LV, Kaiser L, Matrosovich MN, Soo-Hoo Y, Hayden FG. Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis 2001; 183: 523-31. Epub 2001 Jan 11. Abstract: http://amedeo.com/lit.php?id=11170976 - Full text at http://www.jour nals.uchicago.edu/JID/journal/issues/v183n4/000943/000943.html
  16. Hayden FG, Treanor JJ, Fritz RS, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA 1999a; 282: 1240-6. Abstract: http://amedeo.com/lit.php?id=10517426 - Full text at http://jama.ama-assn.org/cgi/content/full/282/13/1240
  17. Hayden FG, Atmar RL, Schilling M, et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med 1999b; 341: 1336-43. Abstract: http://amedeo.com/lit.php?id=10536125 - http://content.nejm.org/cgi/content/full/341/18/1336
  18. Hayden FG, Jennings L, Robson R, et al. Oral oseltamivir in human experimental influenza B infection. Antivir Ther 2000; 5: 205-13. Abstract: http://amedeo.com/lit.php?id=11075941
  19. Hayden FG, Belshe R, Villanueva C, et al. Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis. J Infect Dis 2004; 189: 440-9. Abstract: http://amedeo.com/lit.php?id=14745701 - Full text at http://www.journals.uchicago.edu/JID/journal/issues/v189n3/31422/31422.html
  20. He G, Massarella J, Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet 1999; 37: 471-84. Abstract: http://amedeo.com/lit.php?id=10628898
  21. Herlocher ML, Truscon R, Elias S, et al. Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis 2004; 190: 1627-30. Abstract: http://amedeo.com/lit.php?id=15478068
  22. Hill G, Cihlar T, Oo C, et al. The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies. Drug Metab Dispos 2002; 30: 13-9. Abstract: http://amedeo.com/lit.php?id=11744606 - Full text at http://dmd.aspetjournals.org/cgi/content/full/30/1/13
  23. Hurt AC, Barr IG, Durrant CJ, Shaw RP, Sjogren HM, Hampson AW. Surveillance for neuraminidase inhibitor resistance in human influenza viruses from Australia. Commun Dis Intell 2003; 27: 542-7. Abstract: http://amedeo.com/lit.php?id=15508516
  24. Hurt AC, Barr IG, Hartel G, Hampson AW. Susceptibility of human influenza viruses from Australasia and South East Asia to the neuraminidase inhibitors zanamivir and oseltamivir. Antiviral Res 2004; 62: 37-45. Abstract: http://amedeo.com/lit.php?id=15026200
  25. Ives JA, Carr JA, Mendel DB, et al. The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo. Antiviral Res 2002; 55: 307-17. Abstract: http://amedeo.com/lit.php?id=12103431
  26. Johnston SL, Ferrero F, Garcia ML, Dutkowski R. Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma. Pediatr Infect Dis J 2005; 24: 225-32. Abstract: http://amedeo.com/lit.php?id=15750458
  27. Kaiser L, Wat C, Mills T, Mahoney P, Ward P, Hayden F. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med 2003; 163: 1667-72. Abstract: http://amedeo.com/lit.php?id=12885681 - Full text at http://archinte.ama-assn.org/cgi/content/full/163/14/1667
  28. Kaji M, Fukuda T, Tanaka M, Aizawa H. A side effect of neuraminidase inhibitor in a patient with liver cirrhosis. J Infect Chemother 2005; 11: 41-3. Abstract: http://amedeo.com/lit.php?id=15729487
  29. Kawai N, Ikematsu H, Iwaki N, et al. Factors influencing the effectiveness of oseltamivir and amantadine for the treatment of influenza: a multicenter study from Japan of the 2002-2003 influenza season. Clin Infect Dis 2005; 40: 1309-16. Epub 2005 Mar 16. Abstract: http://amedeo.com/lit.php?id=15825034
  30. Kemink SA, Fouchier RA, Rozendaal FW, et al. A fatal infection due to avian influenza-A (H7N7) virus and adjustment of the preventive measures. Ned Tijdschr Geneeskd 2004; 148: 2190-4. Abstract: http://amedeo.com/lit.php?id=15559415
  31. Kim CU, Lew W, Williams MA, et al. Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors. J Med Chem 1998; 41: 2451-60. Abstract: http://amedeo.com/lit.php?id=9651151
  32. Kim CU, Chen X, Mendel DB. Neuraminidase inhibitors as anti-influenza virus agents. Antivir Chem Chemother 1999; 10: 141-54. Abstract: http://amedeo.com/lit.php?id=10480735
  33. Kirkbride HA, Watson J. Review of the use of neuraminidase inhibitors for prophylaxis of influenza. Commun Dis Public Health 2003; 6: 123-7. Abstract: http://amedeo.com/lit.php?id=12889291
  34. Kiso M, Mitamura K, Sakai-Tagawa Y, et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 2004; 364: 759-65. Abstract: http://amedeo.com/lit.php?id=15337401
  35. Koopmans M, Wilbrink B, Conyn M, et al. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet 2004; 363: 587-93. Abstract: http://amedeo.com/lit.php?id=14987882
  36. Le QM, Kiso M, Someya K, et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature 2005; 437: 1108. Abstract: http://amedeo.com/lit.php?id=16228009
  37. Leneva IA, Roberts N, Govorkova EA, Goloubeva OG, Webster RG. The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Antiviral Res 2000; 48: 101-15. Abstract: http://amedeo.com/lit.php?id=11114412
  38. Lew W, Chen X, Kim CU. Discovery and development of GS 4104 (oseltamivir): an orally active influenza neuraminidase inhibitor. Curr Med Chem 2000; 7: 663-72. Abstract: http://amedeo.com/lit.php?id=10702632
  39. Lin JT, Yu XZ, Cui DJ, et al. A multicentre, randomized, controlled trial of oseltamivir in the treatment of influenza in a high-risk Chinese population. Curr Med Res Opin 2006; 22: 75-82. Abstract: http://amedeo.com/lit.php?id=16393433
  40. Machado CM, Boas LS, Mendes AV, et al. Use of Oseltamivir to control influenza complications after bone marrow transplantation. Bone Marrow Transplant 2004; 34: 111-4. Abstract: http://amedeo.com/lit.php?id=15094755
  41. Massarella JW, He GZ, Dorr A, Nieforth K, Ward P, Brown A. The pharmacokinetics and tolerability of the oral neuraminidase inhibitor oseltamivir (Ro 64-0796/GS4104) in healthy adult and elderly volunteers. J Clin Pharmacol 2000; 40: 836-43. Abstract: http://amedeo.com/lit.php?id=10934667
  42. McClellan K, Perry CM. Oseltamivir: a review of its use in influenza. Drugs 2001; 61: 263-83. Abstract: http://amedeo.com/lit.php?id=11270942
  43. McCullers JA. Effect of antiviral treatment on the outcome of secondary bacterial pneumonia after influenza. J Infect Dis 2004; 190: 519-26. Epub 2004 Jun 30. Abstract: http://amedeo.com/lit.php?id=15243927 - Full text at http://www.journa ls.uchicago.edu/JID/journal/issues/v190n3/32166/32166.html
  44. McGeer AJ, Lee W, Loeb M, et al. Adverse effects of amantadine and oseltamivir used during respiratory outbreaks in a center for developmentally disabled adults. Infect Control Hosp Epidemiol 2004; 25: 955-61. Abstract: http://amedeo.com/lit.php?id=15566030
  45. McKimm-Breschkin J, Trivedi T, Hampson A, et al. Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir. Antimicrob Agents Chemother 2003; 47: 2264-72. Abstract: http://amedeo.com/lit.php?id=12821478 - Full text at http://aac.asm.org/cgi/content/full/47/7/2264?pmid=12821478
  46. McNicholl IR, McNicholl JJ. Neuraminidase inhibitors: zanamivir and oseltamivir. Ann Pharmacother 2001; 35: 57-70. Abstract: http://amedeo.com/lit.php?id=11197587
  47. Nicholson KG, Aoki FY, Osterhaus AD, et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet 2000; 355: 1845-50. Abstract: http://amedeo.com/lit.php?id=10866439
  48. Nordstrom BL, Oh K, Sacks ST, L'Italien GJ. Skin reactions in patients with influenza treated with oseltamivir: a retrospective cohort study. Antivir Ther 2004; 9: 187-95. Abstract: http://amedeo.com/lit.php?id=15134180
  49. Oo C, Barrett J, Hill G, et al. Pharmacokinetics and dosage recommendations for an oseltamivir oral suspension for the treatment of influenza in children. Paediatr Drugs 2001; 3: 229-36. Abstract: http://amedeo.com/lit.php?id=11310719
  50. Oo C, Barrett J, Dorr A, Liu B, Ward P. Lack of pharmacokinetic interaction between the oral anti-influenza prodrug oseltamivir and aspirin. Antimicrob Agents Chemother 2002; 46: 1993-5. Abstract: http://amedeo.com/lit.php?id=12019123 - Full text at http://aac.asm.org/cgi/content/full/46/6/1993?pmid=12019123
  51. Oo C, Hill G, Dorr A, Liu B, Boellner S, Ward P. Pharmacokinetics of anti-influenza prodrug oseltamivir in children aged 1-5 years. Eur J Clin Pharmacol 2003; 59: 411-5. Abstract: http://amedeo.com/lit.php?id=12910331
  52. Peters PH Jr, Gravenstein S, Norwood P, et al. Long-term use of oseltamivir for the prophylaxis of influenza in a vaccinated frail older population. J Am Geriatr Soc 2001; 49: 1025-31. Abstract: http://amedeo.com/lit.php?id=11555062
  53. Risebrough NA, Bowles SK, Simor AE, McGeer A, Oh PI. Economic evaluation of oseltamivir phosphate for postexposure prophylaxis of influenza in long-term care facilities. J Am Geriatr Soc 2005; 53: 444-51. Abstract: http://amedeo.com/lit.php?id=15743287
  54. Rothberg MB, Bellantonio S, Rose DN. Management of influenza in adults older than 65 years of age: cost-effectiveness of rapid testing and antiviral therapy. Ann Intern Med 2003; 139: 321-9. Abstract: http://amedeo.com/lit.php?id=12965940 - Full text at http://www.annals.org/cgi/reprint/139/5_Part_1/321.pdf
  55. Sander B, Gyldmark M, Hayden FG, Morris J, Mueller E, Bergemann R. Influenza treatment with neuraminidase inhibitors Cost-effectiveness and cost-utility in healthy adults in the United Kingdom. Eur J Health Econ 2005; 6: 244-52. Abstract: http://amedeo.com/lit.php?id=15875227
  56. Sato M, Hosoya M, Kato K, Suzuki H. Viral shedding in children with influenza virus infections treated with neuraminidase inhibitors. Pediatr Infect Dis J 2005; 24: 931-2. Abstract: http://amedeo.com/lit.php?id=16220098
  57. Schmidt AC. Antiviral therapy for influenza : a clinical and economic comparative review. Drugs 2004; 64: 2031-46. Abstract: http://amedeo.com/lit.php?id=15341496
  58. Shijubo N, Yamada G, Takahashi M, Tokunoh T, Suzuki T, Abe S. Experience with oseltamivir in the control of nursing home influenza A outbreak. Intern Med 2002; 41: 366-70. Abstract: http://amedeo.com/lit.php?id=12058885
  59. Snell P, Dave N, Wilson K, et al. Lack of effect of moderate hepatic impairment on the pharmacokinetics of oral oseltamivir and its metabolite oseltamivir carboxylate. Br J Clin Pharmacol 2005; 59: 598-601. Abstract: http://amedeo.com/lit.php?id=15842560
  60. Stiver G. The treatment of influenza with antiviral drugs. CMAJ 2003; 168: 49-56. Abstract: http://amedeo.com/lit.php?id=12515786 - Full text at http://www.cmaj.ca/cgi/content/full/168/1/49
  61. Tai CY, Escarpe PA, Sidwell RW, et al. Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071. Antimicrob Agents Chemother 1998; 42: 3234-41. Abstract: http://amedeo.com/lit.php?id=9835519 - Full text at http://aac.asm.org/cgi/content/full/42/12/3234?pmid=9835519
  62. Takahashi K, Furuta Y, Fukuda Y, et al. In vitro and in vivo activities of T-705 and oseltamivir against influenza virus. Antivir Chem Chemother 2003; 14: 235-41. Abstract: http://amedeo.com/lit.php?id=14694986
  63. Tamiflu (package insert). Gilead Sciences, Foster City, 2005. Accessed on 8 January 2005 from http://www.rocheusa.com/products/tamiflu/pi.pdf
  64. Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. JAMA 2000; 283: 1016-24. Abstract: http://amedeo.com/lit.php?id=10697061 - Full text at http://jama.ama-assn.org/cgi/content/full/283/8/1016
  65. Tumpey TM, Garcia-Sastre A, Mikulasova A, et al. Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus. Proc Natl Acad Sci U S A 2002; 99: 13849-54. Abstract: http://amedeo.com/lit.php?id=12368467 - Full text at http://www.pnas.org/cgi/content/full/99/21/13849
  66. Ward P, Small I, Smith J, Suter P, Dutkowski R. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother 2005; 55: Suppl 1: Abstract: http://amedeo.com/lit.php?id=15709056
  67. Welliver R, Monto AS, Carewicz O, et al. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA 2001; 285: 748-54. Abstract: http://amedeo.com/lit.php?id=11176912 - Full text at http://jama.ama-assn.org/cgi/content/full/285/6/748
  68. Whitley RJ, Hayden FG, Reisinger KS, et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001; 20: 127-33. Abstract: http://amedeo.com/lit.php?id=11224828
  69. Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian influenza A (H5N1) infection in humans. N Engl J Med 2005; 353: 1374-85. http://amedeo.com/lit.php?id=16192482 - Full text at http://content.nejm.org/cgi/content/extract/353/13/1374
  70. Woodhead M, Lavanchy D, Johnston S, Colman P, Fleming D. Neuraminidase inhibitors: progress in the management of influenza. Int J Clin Pract 2000; 54: 604-10. Abstract: http://amedeo.com/lit.php?id=11220989
  71. Yen HL, Herlocher LM, Hoffmann E, et al. Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility. Antimicrob Agents Chemother 2005; 49: 4075-84. Abstract: http://amedeo.com/lit.php?id=16189083
  72. Yen HL, Monto AS, Webster RG, Govorkova EA. Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. J Infect Dis 2005; 192: 665-72. Abstract: http://amedeo.com/lit.php?id=1602813
 

 

Department of Biochemistry, The Chinese University of Hong Kong © 2006