???????? ????????? ?-????????????? (Richard T. Kershen et al., 2004) - PowerPoint PPT Presentation

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???????? ????????? ?-????????????? (Richard T. Kershen et al., 2004)

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Title: Author: IRINA Last modified by: Created Date: 8/1/2006 7:50:43 AM Document presentation format: Company – PowerPoint PPT presentation

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Title: ???????? ????????? ?-????????????? (Richard T. Kershen et al., 2004)


1
???????? ????????? ?-????????????? (Richard T.
Kershen et al., 2004)
  ????-??????? ?????-????? ????-??????? ????-??????? ???????
????????????? ? ???????? ???????????? ?????????? M3gtM2 M3gtM2 M3gtgtM2 M3gtM2 M3M2
????????? ??????-??? ???? ??????-??? ???? ??????-??? ???? ??????-??? ???? ??????-?????? ????
?????????? ? ?????? ???? ???? ???? ???? Min
???????? ?????????? ???? ???? ??? ????-?????? ???
2
???????? ?-????????????? ? ????????????
?????????? (??????? M1,M2,M3)
?-??????????? M1 M2 M3
??????? ?????? 9,1 9,2 9,3
?????????? 8,8 8 8,5
??????????? 8,7 7,8 8,9
??????????? 8,2 7,4 9,1
??????????? 7,6 6,9 8
Ensing et al., Brynne et al.
3
???????? ??????? ?-????????????? (Richard T.
Kershen et al., 2004)
  ????-??????? ?????-????? ????-??????? ????-??????? ???????
??????? ?? ??? 87 30 35 21 22
????????? ?????? (????? ???????????) 2 1 ??????? ???????? ? Placebo 6 ??????? ???????? ? Placebo
??????????? (?????????? ????????) 40 ?? ??????? ???????? ? Placebo ??? ?????? ??????? ???????? ? Placebo
4
????????????? ?????????
???????? ???????? log P
Tolterodine 1,83 Rovner 2005
S-Oxybutynin 3,33 Luner ez al. 2001
Darifenacin 2,7 Chapple 2004
Trospium chloride 1,22 Doroshyenko et al. 2005
??????? ????????????? ? ?????
??????????????? ? ?????
log P n-Octanol/puffer ??????????? ?????????????
??????? ????????????? (????? ??????? log P
???????? ????? ??????? ?????????????)
5
?????????????? ?????????
???????? ???????? ????????????? ? ????
Tolterodine 12 mg / ml Rovner 2005
Oxybutynin 0.8 mg / ml Pharm. List
Darifenacin 6.03 mg / ml Chapple 2004
Trospium chloride 500 mg / ml Doroshyenko et al. 2005
6
????????? ???????? ????????
???????????? ???????????
????????? ???????.
????????? ????????
????????. ???????
????????? ???
? ??/?? ????????
??????????????
????????????
???????? ????
????????????
??????? ?? ???
??????? ????
???????????
??????? ????
???? ? ?????
???????????
??????????
??????????
?????????
???????
Trospium chloride
???!
X
X
X
X
X
X
X
Oxybutynin
X
X
X
X
X
X
X
X
X
X
X
X
Tolterodine
X
X
X
X
X
X
X
X
X
X
X
X
X
Propiverin
X
X
X
X
X
X
X
X
X
X
Flavoxate
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Solifenacin
7
?????????? ?-?????????????
??? ????????? ???????????? ?????????? ? ??????
Oxybutynin
Tolterodine
Propiverine
Solifenacin
Darifenacin
Fesoterodine
Trospium ???!
8
?????????? ???????????????? ?????????? ???
??????? ????
??????????? ?????????? ??????????? ????????
?????????? ???????? ????????? P-450 -
?????????? ? ??????????????????? ???????? -
????????? ? ?????????? ???? 0,1 lt 1 11 gt 80
????????????? ??????????????, ????????? ? ???????????? -
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