"5.2\tFarmakokinetick\u00E9 vlastnosti"@cs . "L\u00E9\u010Div\u00E9 p\u0159\u00EDpravky na b\u00E1zi estrogenu se dob\u0159e vst\u0159eb\u00E1vaj\u00ED k\u016F\u017E\u00ED, sliznicemi a gastrointestin\u00E1ln\u00EDm traktem. Estrogeny p\u0159i pr\u016Fchodu pochvou obch\u00E1zej\u00ED proces \u201Efirst-pass\u201C metabolismu.\nByla uskute\u010Dn\u011Bna 12ti t\u00FDdenn\u00ED randomizovan\u00E1, otev\u0159en\u00E1, v\u00EDced\u00E1vkov\u00E1 studie s\u00A0paraleln\u00EDmi skupinami konan\u00E1 v\u00A0jednom centru, kter\u00E1 zkoumala rozsah systemov\u00E9 absorpce estradiolu z p\u0159\u00EDpravku Vagifem. Subjekty byly randomizov\u00E1ny v\u00A0pom\u011Bru 1:1 a dost\u00E1valy bu\u010F 25\u00A0\u00B5g estradiolu (Vagifem) nebo 10\u00A0\u00B5g estradiolu. Hladiny estradiolu (E2), estronu (E1) a estron-sulf\u00E1tu (E1S) v\u00A0plazm\u011B byly m\u011B\u0159eny v\u00A0tyto dny: v den\u00A0-1 (p\u0159ed d\u00E1vkou), v den 1 (po prvn\u00ED d\u00E1vce), v den 14 (po 14 dnech u\u017E\u00EDv\u00E1n\u00ED 1 jedn\u00E9 d\u00E1vky denn\u011B), v den 82 (p\u0159ed d\u00E1vkou, po 10 t\u00FDdnech u\u017E\u00EDv\u00E1n\u00ED 2x t\u00FDdn\u011B) a v den 83 (po d\u00E1vce, po 10\u00A0t\u00FDdnech l\u00E9\u010Dby 2x t\u00FDdn\u011B). Prim\u00E1rn\u00EDm c\u00EDlem studie biologick\u00E9 dostupnosti byl AUC(0-24) pro hladinu E2 v plazm\u011B (viz tabulka 1): tento parametr indikoval vy\u0161\u0161\u00ED syst\u00E9mov\u00E9 hladiny estradiolu v\u00A0p\u0159\u00EDpad\u011B p\u0159\u00EDpravku Vagifem ve srovn\u00E1n\u00ED s\u00A0z\u00E1kladn\u00ED hladinou v\u00A01., 14. a 83. dnu l\u00E9\u010Dby. Pr\u016Fm\u011Brn\u00E9 hladiny E2 v\u00A0plazm\u011B Cave(0-24) v\u0161ak celkov\u011B ve v\u0161ech \u010Dasov\u00FDch bodech z\u016Fstaly pod 20\u00A0pg/ml. \u00DAdaje ze dne 82 nazna\u010Duj\u00ED, \u017Ee b\u011Bhem dlouhodob\u00E9 udr\u017Eovac\u00ED l\u00E9\u010Dby 2x t\u00FDdn\u011B nedoch\u00E1z\u00ED k\u00A0akumulaci syst\u00E9mov\u00FDch hladin estradiolu (viz tabulka 1). \nTabulka 1\nHodnoty farmakokinetick\u00FDch parametr\u016F koncentrace estradiolu v\u00A0plazm\u011B: Studie VAG-1850\nVagifem 25\u00A0\u00B5g estradiolu\n\t\n\tAUC(0-24)\npg.h/ml\n(geometrick\u00FD pr\u016Fm\u011Br)\n\tCave(0-24)\npg/ml\n(geometrick\u00FD pr\u016Fm\u011Br\n\tDen -1\n\t99,66\n\t4,03\n\tDen 1\n\t476,14\n\t19,84\n\tDen 14\n\t438,87\n\t18,29\n\tDen 82\n\t48,13\n\t2,01\n\tDen 83\n\t225,94\n\t9,41\nHladiny estrogenu pozorovan\u00E9 v\u00A0pr\u016Fb\u011Bhu 12 t\u00FDdn\u016F pod\u00E1v\u00E1n\u00ED p\u0159\u00EDpravku Vagifem nevykazuj\u00ED \u017E\u00E1dnou kumulaci estronu.\nMetabolity estrogenu se vylu\u010Duj\u00ED prim\u00E1rn\u011B mo\u010D\u00ED jako glukuronidy a sulf\u00E1ty.\n"@cs . . . . . . "005.002" .