chronopharmacokinetics

(1)

$#

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-5,7289:1.42

47247055982,907,

(2)

%%$

  3974/:.9433974/:.943   01394380139438   $.450$.450   90723,9434190723,94341 .7.,/,37928 .7.,/,37928   ,881.,943,881.,943   ,.9478,110.93,.9478,110.93 .7.,/,37928 .7.,/,37928   55.,943855.,9438   7:89,9:3/074087:89,9:3/07408 .7434309.8 .7434309.8   43.:84343.:843   #010703.08#010703.08

(3)

3974/:.943

P P $9:/4190902547,.,3083$9:/4190902547,.,3083 P P %031:03.04192041,/23897,943%031:03.04192041,/23897,943 P P 420489,88420489,88 P P 43...,.,3043...,.,30

(4)

0139438

P P 74345,72,.4309.874345,72,.4309.8 P P 44.,79244.,792 P P %0!074/%%0!074/% P P %0.745,80[%0.745,80[ P P %0259:/0%0259:/0 P P %00847%00847 P P %0706:03.%0706:03.

(5)

(6)

7.,/,37928

 4034:87928  4034:87928 $005,0..08-44/57088:70 $005,0..08-44/57088:70 5:80 5:80 7,90209,-4.,8974390893,7928 7,90209,-4.,8974390893,7928   3/4034:879283/4034:87928  %4:95:9.479%4:95:9.479.489074/4:95:9.489074/4:95:9 .7.:,9330:97458.7.:,93 .7.:,9330:97458.7.:,93 04834587,5/0024;02039 04834587,5/0024;02039

(7)

(8)

P P :73,;,7,9438:73,;,7,9438 P P 4.9:93,;,7,94384.9:93,;,7,9438 P P $3.7438,943$3.7438,943 P P 7434-447434-44 P P 74345,72,.4474345,72,.44 P P 74345,72,.4/3,2.874345,72,.4/3,2.8 P P 7434907,57434907,5

(9)

$.450

P P 439749092041,/23897,943439749092041,/23897,943 P P ',7,943835,82,/7:0;0,8,1:3.943',7,943835,82,/7:0;0,8,1:3.943 4192041/, 4192041/, P P 0.,3827085438-014790920/0503/0390.,3827085438-014790920/0503/039 ;,7,943 ;,7,943

(10)

 

_{030300/.74345,72,.4309.8}

P P ,;,7,943835,72,.4309.8,;,7,943835,72,.4309.8 P P ,774907,50:9.7,30,774907,50:9.7,30 P P $25942841,/80,80 .7.,/,35,80$25942841,/80,80 .7.,/,35,80 /0503/039 /0503/039

(11)

,88.5,802,7078 ,88.5,802,7078 P P 0,943380.70943-90530,,3/0,943380.70943-90530,,3/ P P 470-4/902507,9:70470-4/902507,9:70

(12)

,881.,943

P P !844.,3/:.0/920/0503/03.!844.,3/:.0/920/0503/03. P P 02.,3/:.0/920/0503/03.02.,3/:.0/920/0503/03.

(13)

!844.,3/:.0/920

/0503/03.

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P P -8475943023,9435,7,209078-8475943023,9435,7,209078 P P 897-:943897-:943 P P 32,9.209,-4.,.9;932,9.209,-4.,.9;9 P P $8902..0,7,3.0$8902..0,7,3.0 P P #03,.0,7,3.0#03,.0,7,3.0 P P $/7:.43.0397,943$/7:.43.0397,943 P P !,82,-3/3!,82,-3/3

(14)

7.,/,3.,3083/7:

,-8475943

  ,897.,./80.70943,897.,./80.70943   55   499499   ,897.02593920 43071470;03320, ,897.02593920 43071470;03320, 9 9_2,_2,   ,8974390893,-44/14,8974390893,-44/14

(15)

  !8.4.02.,574507908 545.947!8.4.02.,574507908 545.947 /745.9 /745.9 ,2508 ,2508   47545./7:847545./7:8!03943!03943 1,8907 1,8907 ,-847594339024733 ,-847594339024733   $8 $8 3/4209,.3,3/0945741033/4209,.3,3/094574103 -09907,-847594339024733,3/70,907 -09907,-847594339024733,3/70,907 -4,;,,-9 -4,;,,-9  !,7,.09,24!,7,.09,24  0903941,-84759438088,9  0903941,-84759438088,9

(16)

7.,/,3.,3083/7:/897-:943

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(17)

7.,/,3.,30835,82,574903

-3/341/7:8

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(18)

7.,/,3.,3083/7:209,-482

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(19)

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P P 05,9.-44/1405,9.-44/14 3/4.,330 70033/4.,330 7003  __ _{.0,7,3.0}_{.0,7,3.0} P P %%02547,;,7,94334/,80 02547,;,7,94334/,80 ,.9;94190,.9;94190

(20)

 

_{29,94384190209,-482}

  ,5,.9290/209,-482 /0.70,808,5,.9290/209,-482 /0.70,808 05,9..0,7,3.03.,8041 05,9..0,7,3.03.,8041!03943!03943   3203/:.9433203/:.943 ,7-,2,0530,7-,2,0530  05,9..0,7,3.0 05,9..0,7,3.0   0.70,80/05,9.-44/140.70,80/05,9.-44/14 !7457,3,4!7457,3,4   05,9..0,7,3.0 05,9..0,7,3.0 4397,3/.,9438 4397,3/.,9438   434403,80,.434403,80,.9;908 9;908 2,0,3/1022,0,3/102,0,0 7,98 7,98   ;072.74842,908948907430/74,80;072.74842,908948907430/74,80

(21)

%20/0503/,3.388902..0,7,3.0

P P

88902..0,7,3.0

//

0.70,808,939

,3

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_{3.70,808}

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_{,920}

P P

47

//

7:894097,.9437,948

1:.9:,9438339738.209,-4.

.0,7,3.035,82,574903-3

//

_3

(22)

7.,/,3.,3083/30/7:

0.70943

P P 4207:,7197,9434207:,7197,943 P P #03,-44/14#03,-44/14 P P &73,75&73,75 P P %:-:,770,-8475943%:-:,770,-8475943 P P &7304:95:9,3/&7304:95:9,3/ P P &73,70.709434100.974908&73,70.709434100.974908

(23)

%0792.93:73,75 %0792.93:73,75 24/108/7:43,943 24/108/7:43,943 P P ././7:8,700.7090/1,8907,19070;033././7:8,700.7090/1,8907,19070;033 ,/23897,943 ,/23897,943  $4/:28,.,90$4/:28,.,90 ,3/,3/$:1,82,30$:1,82,30

(24)

%20/0 %20/0503/03.3.07503/03.3.070-74853,1:/0-74853,1:/.81/7:.81/7: .43.0397,943 .43.0397,943 P P ,2,/:7390/,75074/ ,2,/:7390/,75074/  ,24:78 ,24:78 P P 32,/:739095074/ 32,/:739095074/  524:78 524:78

(25)

02.,3/:.0/920/0503/03.

P P :943/:.943:943/:.943  ,7-,2,0530#1,225.309.,7-,2,0530#1,225.309. P P :943-943:943-943 ,39304/,803-947 ,45:734 ,39304/,803-947 ,45:734

(26)

,.9478,110.93.7.,/,37928

P P 44/44/ P P 0,9230,923 P P ,8974390893,5,8974390893,5 P P 390893,2499390893,2499 P P 089;080.709438089;080.709438 P P 390893,-44/14390893,-44/14 P P 99

(27)

P P %0923410548:70949%0923410548:70949 P P %0039410548:70%0039410548:70 P P 390389,3/,;0039419390389,3/,;0039419

(28)

!,8070854380.:7;0

(29)

 _{9071,.9478}_{9071,.9478} P P !8.,,.9;9!8.,,.9;9 P P :8.:8. P P /23897,943419030:74472430/23897,943419030:74472430 20,9433 20,9433 P P 00/38.0/:0800/38.0/:08 P P %02507,9:70%02507,9:70 P P !,72,.44!,72,.44

(30)

55.,9438

P P 892,892,   4.9:73,47804.9:73,47803341,892,3341,892,8,8074:88,8074:8 .3.,574-02 .3.,574-02   ;033;033 %04530%04530 ,3/,3/×,4389×,4389 -743.4/,947 -743.4/,947 P P !059.:.07!059.:.07  

247335749435:253-947

 

0;033

__

70.05947

,39,4389

(31)

P P ,3.07,3.07 P P 507903843507903843 07.43.0397,94380,724733 07.43.0397,94380,724733

(32)

 

_{7:89,9:3/074.7434309.8}

P P 39-49.8 39-49.8 234.48/08234.48/08 P P 395079038;0395079038;0/7:8 /7:8 !7457,344!7457,344 10/530 10/530 P P 3905059./7:83905059./7:8 '',,547.547.,,././ P P 39.,3.07/7:8 39.,3.07/7:8   .4854730094970 .4854730094970 ,,9090 P P $$8 8   0945741033/42090945741033/4209,,.3.3

(33)

 

_{29,94341920/0503/0395,72,.4309.8}

P P 110703.0-09003850.08 74/0398 ,3/110703.0-09003850.08 74/0398 ,3/ :2,38 :2,38 P P ,721:9474/039805072039,,32,,721:9474/039805072039,,32, P P ,703:2-0741,32,8,703:2-0741,32,8 P P '07.4250 ,39.,3.07/7:'07.4250 ,39.,3.07/7:

(34)

(35)

#

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