1.

ASARKIN 1 mg

2.

1 mg ( ).

, . 6.1

3.

, ( 11,5 mm x 6 mm), ,
R9SE 1 .

4.

4.1

ASARKIN Parkinson (PD)

( ) ( )
.

4.2

, 1 mg
.

ASARKIN

( 4.3).
.
.
 ,
( 4.4).

4.3

( 6.1).

() (
.. St.Johns Wort)
( 4.5). 14
.

4.4

( 4.5).
.
14
.

(ICDs)
/ .

.
.

,
, ,
, , ,
.

,
.
.

.

.

( 4.5).

.
Parkinson
,
 ( ).
.

.
.
, (
5.2).

4.5

(
.. St.Johns Wort)
, ( 4.3).

-.
( 4.3).

.
,


, ( 4.4).

. ,
,
( 4.4).

.( 4.4).

(SSRIs)/
(SNRIs) , 4.8.
SSRIs,
SNRIs, , . ,
,
.

,
.

in vitro P450 12 (CYP1A2)

.
( CYP1A2) AUC
83%. (
CYP1A2) . ,
CYP1A2
.

, CYP1A2.

in vitro 1 g/ml (
160 Cmax ~ 5,9-8,5 ng/ml
1 mg ),
450, CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 CYP4A.


.

28%.

(
),
( 464 0,5 1 mg/

),
/
,
.

4.6 ,

.
, , (
5.3). .

,
.
. .

4.7

, ,
ASARKIN .

4.8

1.361
3.076,4 /. ,
, 529 1 mg/ 212 /
539 213 /.

1 mg/ ( n=149,
n=151).

2%
.
(% ) (vs.) ,
.

: (1/10), (1/100 <1/10),
(1/1.000 <1/100), (1/10.000 <1/1.000),
(<1/10.000).

: (4,7% vs. 0,7%)
, (
)
: (1,3% vs. 0,7%)

: (1,3% vs. 0%)

: (1,3% vs. 0,7%)

: (0,7% vs. 0%)

: (5,4% vs. 2%), (1,3% vs. 0,7%)

: (14,1% vs. 11,9%)
: (0,7% vs. 0%)

: (2,7% vs. 0,7%)

: (2,7% vs. 1,3%)

: (1.3% vs. 0%)
: (0.7% vs. 0%)
,
: (3,4% vs. 0,7%)

: (1,3% vs. 0%)

: (2,0% vs. 0%)
: (0,7% vs. 0%)

: (6,7% vs. 2,6%), (2,7% vs. 0%), (1,3% vs.
0,7%)

: (1,3% vs. 0,7%)

: (2,7% vs. 1,3%), (2% vs. 0%)

,

1 mg/ ( n=380,
n=388). (% )
(vs.) , .

2%
.

: (1/10), (1/100 <1/10),
(1/1.000 <1/100), (1/10.000 <1/1.000), (<1/10.000).

,
: (0,5% vs. 0,3%)

: (2,4% vs. 0,8%)

: (2,9% vs. 2,1%), (2,1% vs. 0,8%)
: (0,8% vs. 0,5%)

: (10,5% vs. 6,2%)
: (2,4% vs. 0,8%), (1,3% vs. 0%),
(1,6% vs. 0,3%)
: (0,5% vs. 0,3%)

: (0.5% vs. 0%)

: (3,9% vs. 0,8%)

: (4,2% vs. 1,3%), (4,2% vs. 2,1%), (8,4% vs.
6,2%), (3,4% vs. 1,8%)

: (1,1% vs. 0,3%)

: (2,4% vs. 2,1%), (1,3% vs. 0,5%)

: (4,5% vs. 1,5%)

,
: (4,7% vs. 3,4%)

.

.

SSRIs, SNRIs,,
. ,
, , , ,
/SNRIs .


: 50 mg/,
100 mg/, 20 mg/, 100
mg/ 30 mg/ .
115
141 SSRIs/SNRIs,
.

,

.

.
,

.

, , ,
,
/
.
,
, ( 4.4).

.
- .

, 284 GR-15562 , ,
: + 30 21 32040380/337, : + 30 21 06549585, : http://www.eof.gr

4.9

:
3 mg 100 mg , ,
.

-
-. , 20 mg/
10 mg/.
.
,
10 mg/ ,
(
) .

.
 . ,

.

5.

5.1

: ,
-
ATC: 04D02

,
-,
.


.
1-
-.

:
.

, 404 (138
), 1 mg/ (134 ) 2 mg/ (132 )
26 .
,

Parkinson (UPDRS, I-III).
26/ (LOCF, Last Observation
Carried Forward) (UPDRS, I-III: 1 mg
-4,2, 95% CI [5,7, -2,7], p<0,0001, 2 mg
-3,6, 95% CI [-5,0, -2,1];p<0.0001 UPDRS Motor, :
1 mg 2,7, 95% Cl [-3,87, -1,55], p<0.0001,
2 mg 1,68, 95% Cl [-2,85, -0,51],
p=0,0050). ,
.
( PD-QUALIF).

, (229
) 1 mg/ (231 ) -O--
(COMT), , 200 mg
(LD)/ (227 )
18 . ,
(159 ), 0,5 mg/ (164 ) 1
mg/ (149 ) 26 .


 OFF (
24 3
).

,
OFF 0,78 , 95% CI [-1,18, -0,39], p=0.0001.
OFF
(-0,80h, 95% CI [-1,20, -0,41], p<0,0001)
1 mg. ,
-0.94h, 95% CI [-1,36, -0,51], p<0,0001.
, ,
0,5 mg, .

(
() , () ).

,
(ADL) OFF UPDRS motor .
.

5.2

,
(Cmax) 0,5 .
36%.
max Cmax (AUC)
60% 20% ,
.
AUC ,
.

243 L.

14C 60% 70%.

.
: N- /
: 1-, 3--N--1
3--1-. in vitro
P450, CYP1A2
.

.

14C,
(62,6%)
(21,8%), 84,4%
38 . 1%
.

/
H 0,5-2 mg.
0,6-2 .

: , AUC
Cmax 80% 38% .
, AUC Cmax 568% 83% (
4.4).

:
(CLcr 50-80 ml/min) (CLcr 30-49 ml/min)
.

5.3

, ,
.

in vivo in vitro
. ,

,
.

, ,
84-339 ,
1 mg/. ,
/ /
144-213
1 mg/.

6.

6.1

Cellulose, microcrystalline
Tartaric acid
Maize starch
Starch, pregelatinized maize
Talc
Stearic acid

6.2

6.3

30

6.4

25C.
6.5

blister oPA/Al/PVC/Al 7, 10, 28, 30, 100 112 .

blister PVC/PVDC/Al 7, 10, 28, 30, 100 112 .

6.6

7.

.., , 14671 , . 210 8009111-120

8. ()

14269/15/05-09-2016

9. /

: 05-09-2016

10.

05-09-2016