Вы находитесь на странице: 1из 4

interaction3:Layout 1 12/5/12 1:00 AM Page 1

.., .., .. , ..,


.., ..

HCV
, () 50-60% ( 40-50%
1 ). 1 (
70 %), ,

[9]. ,
, .

HCV- 1
4-21 % .
,
,
, .

: , HCV, -
NS5B , NS5A , , [18].
NS3/4A - .

[1].
,
,
. 1

, [10, 11, 24, 28].



450
NS3/4A .
,
.

HCV 1 , 12 ,
. ,
.
, ,
( , , ).
, 450,
, / . (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1,
CYP3A4), de
novo ,

[16]. 60 % ()
CYP3A4, , ,
,
CYP2D6 [23].

, 2012, 3

interaction3:Layout 1 12/5/12 1:00 AM Page 2

1.

(TVR)

: , .
: ,

()

TVR, : ,
TVR, :

S-

: ,

: TVR

, , TVR. , : 200 /.

, , , ,

: , .

, ,

, , :

TVR:

:

/
:

b2-

a,

a/

CYP3A4 ,
.

.
,

[20].
450
,
,
.

CYP3A4.
[12]. In vitro
CYP1A2, CYP2C9, CYP2C19, CYP2D6.
CYP3A4 2

:
,
.

(. 1) [27].
,
,
. a-2
CYP1A2, CYP3A4, HCV.


-. [15].


CYP3A4,
, , .

, 2012, 3

interaction3:Layout 1 12/5/12 1:00 AM Page 3


. CYP3A4
[5,6]. CYP3A4
16 . (750
) (600 1
), 92 % [6].


, [11].

. , , [3].
, , 2- ,
.
.
.


HCV-


[28]. , , - (
, ),

. , ,
HCV- .


(n=15) (n=6) [13].

CYP3A4
.
:

1,27 ,
41,3 95,1 .

CYP3A4 [7].
.
10,6 , -. -
, ,
CYP3A4.
, . ,



.

.
,
[13].

6 , .
,
.

,
CYP3A4.
1- 24 . ,
28%, , ,
. [4].
,
,
.
- 12
. 30 %
1 . -
() [8,17]. ,
. CYP3A4.
S- 10 .

41 % [25]. , c
-

HCV 100 %
[21].


. ,
.

CYP3A4
- [14, 19, 22, 29]. 20 .

, 2012, 3

interaction3:Layout 1 12/5/12 1:00 AM Page 4


100 2 /, .
750 8
12 .
10 0.5 . 1,4 ,
- 4 . 9,3 , 5 .

.
,

. ,


, . [26].

,
,
, .

HCV-, (12 ), ,
,
.

1. Arasappan A, Padilla AI, Jao E et al. Toward second generation hepatitis C


virus NS3 serine protease inhibitors: discovery of novel P4 modified analogues with improved otency and pharmacokinetic profile J Med Chem
2009; 52: 280617.
2. Chevaliez S, Pawlotsky . Chapter 1: HCV genome and life cycle. In:
Hepatitis C Viruses Genomes and Molecular Biology. E-Book.
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=hcv (2 February
2010, date last accessed)
3. Cacoub, P., Bourliere, ., Lubbe, J., et al. Dermatologial side effects of
hepatitis C and its treatment: Patient management un the era of direct-acting antivirals. J. Hepatology, 2011, doi:10.1016|j.jhep.2011.08.006.
4. Garg V, et al. The Pharmacokinetic Interaction Between an Oral
Contraceptive Containing Ethinyl Estradiol and Norethindrone and
Telaprevir. IWCPHT 2011. Abstract PK_17 P. 19
5. Garg, V. The Effect of Low-dose Ritonavir on the Pharmacokinetics of the
HCV Protease Inhibitor Telaprevir in Healthy Volunteers PK_15 .17
6. Garg, V. et al. The effect of CYP3A inhibitors and inducers on the pharmacokinetics of telaprevir. IWCPHT 2011. Abstract PK_13 P.15

7. Glesby MJ, Aberg JA, Kendall MA, Fichtenbaum CJ, Hafner R, Hall S,
Grosskopf N, Zolopa AR, Gerber JG; Adult AIDS Clinical Trials Group
A5159 Protocol Team. 2005. Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers. Clin Pharmacol Ther.
78:143-53. 382.
8. Gleason O.C, Yates W.R., Philipsen M.A. Mayor depressive disorder in
hepatitis C: an open-label of escitalopram. Prim. Care Companion J. Clin.
Psychiatry., 2005, 7 (5), 225-230
9. Hoofnagle J., Seeff L. Peginterferon and ribavirin for chronic hepatitis C. N.
Engl. Med., 2006, 355, 2444-2451
10. Jacobson IM, McHutchison JG,Dusheiko GM, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med
2011;364:2405-2416
11. Jacobson IM, McHutchison JG, Dusheico JM, et al. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment-nave
patients: final results of Phase 3 ADVANCE study. Hepatology
2010;52(suppl):427A
12. Kempf DJ, Klein C, Chen HJ, et al. Pharmacokinetic enhancement of the
hepatitis C virus protease inhibitors VX-950 and SCH 503034 by co-dosing
with ritonavir. Antivir. Chem. Chemother 2007;18:1637
13. Lee, J E. Et al. The pharmacokinetic interaction between amlodipine or atorvastatin and the HCV protease inhibitor telaprevirPK_14 .16
14. Neoral (Cyclosporine) US Package Insert, 2009. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050715s028,050716s029lbl.pdf
(accessed 31 January, 2011).
15. Mannering G.I., Renton K.W., El_Arhary E., Deloria L.B. // Ann. N.Y.
Acad. Sci., 1980, 50, 314331.
16. Modulation of cytochrome P-450 gene expression in endotoxine mice is tissue specific and peroxisome proliferators receptor A dependent /T. Barclay,
I. Peters, M. Sewer et al. // J. Pharm. Exp. Ther. 1999. Vol. 290. P.
12501257.
17. Raison C. L., Demetrashvili M., Capuron L., Miller A.H. Neuropsychiatric
adverse effects of interferon0alfa^ recognition and management. CNS
Drugs, 2005, 19 (2), 105-123
18. Pawlotsky J., Chevaliez S., Mchutchison J. The hepatitis C virus life cycle
as a target for new antuviral therapies. Gastroenterology, 2007, 132, 19791998
19. Prograf (Tacrolimus) US Package Insert, 2009. http://
www.accessdata.fda.gov/ drugsatfda_docs/ label/2009/050708s027,
050709s021lbl.pdf (accessed31 January, 2011)
20. Testa B. Inhibitors of cytochrome P_450 and their mechanism of action. B.
Testa, P. Lenner. Drug Metabol. Rev., 1981, 12 (1), 1117.
21. Terrault NA. Treatment of recurrent hepatitis C in liver transplant recipients. Clin Gastroenterol Hepatol 2005;3(10 Suppl 2):S125-S131
22. Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T. Human P-glycoprotein
transports cyclosporine and FK506. J Biol Chem 1993;268: 6077-6080.
23. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. Interindividual
variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994;
270(1):414-423.
24. Sherman K., Flamm S., Afdhal N. Et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N. Engl. J.Med., 2011, 265,
1014-1024.
25. Van Heeswijk R, et al. The pharmacokinetic interaction between escitalopram and the investigational HCV protease inhibitor telaprevir. 5th
International Workshop on Clinical Pharmacology of Hepatitis Therapy
2010: Abstract 12.
26. Varun Garg, et al.Effect of Telaprevir on the Pharmacokinetics of
Cyclosporine and Tacrolimus. Hepatology 2011;54:20-27
27. Vertex Pharmaceuticals Inc. Incivek (telaprevir) product information.
Cambridge, MA; 2011.
28. Zeuzem S, Andreone P, Pol S et al. 2011. Telaprevir for retreatment of HCV
infection. N. Engl. J. Med. 2011, 364:2417-2428.
29. Wu CY, Benet LZ. Disposition of tacrolimus in isolated perfused rat liver:
influence of troleandomycin, cyclosporine, and GG918. Drug Metab Dispos
2003;31:1292-1295.

, 2012, 3

Оценить