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- 积分
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- 威望
- 6
- 包包
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INTRODUCTION lism, the challenge still exists to develop an in vitro liver( @6 A" Q) T: @- G' T, \: k
cell system able to effectively predict, in a species-
$ S. K. |- _5 o9 G5 i) `0 [In the last 15 years many different liver cell culture specific manner, the liver toxicity, the biotransformation5 U8 n% Z7 @, [0 [. W7 u
devices, consisting of functional liver cells and artificial reactions, and the potential for interactions of drugs and: ~4 J' T# m% W$ ~. ?2 i( _
materials, have been developed. They have been devised NCEs in the preclinical stage of drug discovery and defor
- V' U- V. \2 Y5 ^numerous different applications, such as temporary velopment.. A: R& b; @* X, c. S$ \5 G% ?
organ replacement (a bridge to liver transplantation or Furthermore, the development of an in vitro screennative, g. l1 e9 e/ w
liver regeneration) and as in vitro screening sys- ing system, based on living human liver cells, might be h* }/ \# w- r- ]1 J
tems in the early stages of the drug development pro- an alternative to animal experimentation. It bypasses the+ F7 l5 w/ j! Z: t) Z4 |6 k1 l4 p
cess, like assessing hepatotoxicity, hepatic drug metabo- lower predictive value of animal models related to siglism! N- y7 |5 \" C
and induction/inhibition studies. nificant interspecies differences and bioethical consider-
2 ~5 W; V9 k( T% I! F& [6 ARecently, an increased number of approved drugs and ations, reducing animal use for research purposes.
3 h( H. ~3 F8 d; _9 ynew chemical entities (NCE) have been withdrawn from Multiple efforts have been made within the scientific [& ~ V; M8 p5 @. V
the market, because of low pharmacokinetics/pharmaco- community in order to find a cell-based system able to; U; I2 I/ ~# f- p0 j) e0 e
dynamics profiles, or serious and unexpected adverse ef- assess human hepatotoxicity of NCEs and new drugs as2 @& W/ C* ~! ?" j: p9 x8 ]- A
fects during postmarketing surveillance phase, leading well to study in vitro hepatic metabolism.
2 Y" r3 K4 p3 Kto high costs and unacceptable prolonged times for drug This review summarizes as much as possible the exdevelopment) K) j. _* f5 L) E
(29,43,97). perimental data regarding two-dimensional (2D) and
( R% m/ K4 o9 n$ U$ mBecause the liver is the key player in drug metabo- three-dimensional (3D) in vitro screening systems based |
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发表于 2010-11-1 13:25
发表于 2011-1-12 11:46
