PDF电子书：Drugs: From Discovery to Approval, 2nd

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- G: C2 E* ]  q, f; r% WDrugs: From Discovery to Approval, 2nd Edition# i, [8 {& @9 h6 L2 V; Y5 Z* }4 C2 @
Rick Ng
2 L$ y3 N% _9 u' u. @% D+ B  K4 d* LNovember 2008, ©2009, Wiley-Blackwell
0 ?, V" D  Q0 w* {9 n) t4 r1 t: Q! _' z: l; j' \* ?4 ~
Table of Contents
' ]! b+ A2 d7 TPREFACE.
5 d5 ]2 M. G: \; @1 INTRODUCTION.
% @: D% W* I2 A; Q. r# @1.1 Aim of This Book.* O$ I& y" w: T: U4 o
1.2 An Overview of the Drug Discovery and Development Process.1 ~2 R( r/ {) B
1.3 The Pharmaceutical Industry.- [& G, M% x2 ~9 ^/ L
1.4 Economics of Drug Discovery and Development.
) J- A4 g& x, ^3 b8 W1.5 Trends in Drug Discovery and Development.8 O9 Q  X# E; w  h$ }
1.6 Case Study #1.: R0 k. h( f4 \- B; e; C7 k
1.7 Summary of Important Points.) h/ c+ K% P3 ~8 R3 R' u
1.8 Review Questions." B  _. j! ]/ y' i, e
1.9 Brief Answers and Explanations.
# p6 C+ K: F. S  W1.10 Further Reading.  P; L/ o/ t6 r0 D5 h
2 DRUG DISCOVERY: TARGETS AND RECEPTORS.8 s  J+ K( T" ~5 K9 ^! O
2.1 Drug Discovery Processes.
. O/ f- e% J4 U/ j9 B2.2 Medical Needs.( [- Z' r& Z0 u: a( F
2.3 Target Identifi cation.
3 R$ T2 H/ b0 p5 E2.4 Target Validation.
( C8 s; K! c5 Q2 V# f! }2.5 Drug Interactions with Targets or Receptors.
' |8 O# s+ [3 N! }2.6 Enzymes.3 x& u" W; e2 Z6 H% U
2.7 Receptors and Signal Transduction.* |( _0 s- m9 H+ H: s2 g5 C) V3 d
2.8 Assay Development.+ V5 e( W$ O$ X0 Q2 B8 Z
2.9 Case Study #2.+ w9 B- _, m( M& N* f% l  A
2.10 Summary of Important Points.
- x7 ?# r! V' v4 K% R; j2.11 Review Questions./ v" W) F1 g8 R# o% W
2.12 Brief Answers and Explanations.1 x' [2 T9 S. Y2 j9 _8 t8 i4 E
2.13 Further Reading.1 R9 T) p5 H: N
3 DRUG DISCOVERY: SMALL MOLECULE DRUGS.
, n3 l7 E7 ~. A4 s7 S7 u3.1 Introduction.
) [/ h' ?7 S, b1 U. J* v3.2 Irrational Approach.
' E' I& i' H1 h* m/ C! [3.3 Rational Approach.
4 z. |* D2 _+ F# \5 Q  V3.4 Antisense Approach.4 c5 I9 N" k* @2 ^% u" P/ i9 g
3.5 RNA Interference Approach.
5 N; L5 R) j- ]/ k4 J9 ]3.6 Chiral Drugs.# t- U6 M; u5 O# V+ w; k
3.7 Closing Remarks.
  e6 F6 w# ~! M7 f+ \2 j1 F3.8 Case Study #3.
! ~2 q  @' B% Y8 k6 X3.9 Summary of Important Points./ n. h# B# ~" Z5 T" I& C+ D9 }4 q
3.10 Review Questions.
4 ?1 N9 o# M' [4 L3.11 Brief Answers and Explanations.
) ]# u- @& c* v% q2 W. t3.12 Further Reading.& G$ f3 }0 P" e" W% f
4 DRUG DISCOVERY: LARGE MOLECULE DRUGS.' W. c1 `& |  R
4.1 Introduction.2 E+ ]+ K' t( q- j, V* Q$ n  z% v
4.2 Vaccines.2 ~( q  ]6 d/ z/ P9 W
4.3 Antibodies.8 h% Y, W/ V4 E6 C& C  Y& w" k2 a: w
4.4 Cytokines.
) g7 r6 ?! W+ x  i3 _4.5 Hormones.
$ W' o4 `6 B0 n) ~9 W7 B% f4.6 Gene Therapy.. a9 z; {! i1 A" a/ m  U% V
4.7 Stem Cells and Cell Therapy.
6 Y7 {$ z2 X* G% N+ L( t. A# f4.8 Case Study #4.7 ~% m' F+ f0 p4 _! L: B/ j
4.9 Summary of Important Points.
3 T9 \2 }/ e% c' u- U3 r9 [4.10 Review Questions.
7 o: w5 a5 n6 K: m# ]4.11 Brief Answers and Explanations.
9 \, a2 v) @) S9 |; K  v( n8 s4.12 Further Reading.7 Z' \: t4 t) E! ^7 G4 D( {
5 DRUG DEVELOPMENT AND PRECLINICAL STUDIES.! w  n7 W4 A' k
5.1 Introduction.
! P2 ]/ J: `: w  F  `& ~5.2 Pharmacodynamics.  @5 Q. C. W# Y$ s$ N+ D  I6 b- i
5.3 Pharmacokinetics.
9 `: X6 r! G1 N5.4 Toxicology.0 U' G: `1 |/ [; y$ r: X& i8 b
5.5 Animal Tests, In Vitro Assays, and In Silico Methods.
% c/ y- ?# @  I$ {# v/ v5 U5.6 Formulations and Delivery Systems." o, t5 @" V9 n7 f
5.7 Nanotechnology.1 S& [* }2 Z) i0 D, ~- k, E
5.8 Case Study #5.3 J+ {# H- y/ i5 L
5.9 Summary of Important Points.8 c- \8 E8 `3 }  \* A
5.10 Review Questions.
$ c9 p  G' }2 H& v8 H5.11 Brief Answers and Explanations." P/ N% f9 `* l' ^
5.12 Further Reading.3 ]  t7 S5 `; h/ k  z& `
6 CLINICAL TRIALS.
/ R: j% |; E: C4 W# E6 o5 T6.1 Defi nition of Clinical Trial.
/ \9 s& Z& e. v' t. u6.2 Ethical Considerations.
: J8 {& _8 S/ x5 q: r! R6.3 Clinical Trials.) u* A) W4 S2 {, E
6.4 Regulatory Requirements for Clinical Trials.
% |  }) Z1 o1 ]6.5 Role of Regulatory Authorities.
7 x3 N+ c( ~6 M; J6.6 Gene Therapy Clinical Trial.
! Z( J$ l9 |. Y# F$ O' c. ~) t6.7 Case Study #6.. h# g% u% f1 d/ T( W# `) F6 f
6.8 Summary of Important Points.
: M9 i" X. k/ n7 ]6.9 Review Questions.
# h: ~! [+ k2 Q/ w6.10 Brief Answers and Explanations.5 ]" n( D; R, s% e" h# k5 v3 v  L
6.11 Further Reading.. w/ \) W2 `4 Z* U" v
7 REGULATORY AUTHORITIES.1 L6 V* Q6 K. S2 ~3 B/ E2 x. Y
7.1 Role of Regulatory Authorities.* T( o& K3 i, A/ |2 O/ W' ~
7.2 US Food and Drug Administration.3 z8 x9 U( B" z1 y. o
7.3 European Medicines Agency.
9 ^9 g* j1 |( K5 v7.4 Japan’s Ministry of Health, Labor and Welfare.
0 v6 }: l! J- q# |5 T3 Y7 @7.5 China’s State Food and Drug Administration.  e: x3 Y1 R- p: g" X
7.6 India’s Central Drugs Standard Control Organization.' h3 p  e) W" j, }, ?( |2 ?
7.7 Australia’s Therapeutics Goods Administration.9 D; l( I: T4 D
7.8 Canada’s Health Canada.
) \; g+ e$ F; C8 d' ]2 t3 H8 B7.9 Other Regulatory Authorities.% R6 B: a. {) ^6 z% k, J! B
7.10 Authorities Other than Drug Regulatory Agencies.
3 h+ a. o1 Y: V1 B: y$ o9 O7.11 International Conference on Harmonization., H; c% d! t% }+ _2 x
7.12 World Health Organization.
# S' ^7 ]$ K3 ]& |4 y6 \) Z7.13 Pharmaceutical Inspection Cooperation Scheme.3 |8 V$ U! D9 x0 e
7.14 Case Study #7.8 t8 g! e4 s# |9 K' z. @
7.15 Summary of Important Points.
/ v$ |& W3 K4 r6 g7.16 Review Questions.$ |1 [$ q8 D7 s& c* W4 u' I8 S5 s+ k
7.17 Brief Answers and Explanations.4 ^% m- y7 f9 T! E4 \+ l9 t
7.18 Further Reading.: [  r+ B/ ^* s* O5 d3 i$ k4 M
8 REGULATORY APPLICATIONS.' r  V% \) O: L; n( l6 Q
8.1 Introduction.; `+ v1 N  {0 M2 V  |. h  ^* m
8.2 Food and Drug Administration.8 ~, w! r& v3 _1 c  Q7 D! G! {7 h
8.3 European Union.
2 ?" T8 C' \; U- X% _8.4 Japan.1 w9 d3 t( K8 p" M
8.5 China." k$ r' ]# P5 U5 t8 p5 M; a
8.6 India.
/ D, b1 S5 @$ \' ^8.7 Australia.- b+ b4 g% i* j3 H9 Y, ~* }: t3 x8 W
8.8 Canada.1 A/ x- X! F% I. H# Q7 v! c
8.9 Case Study #8.
3 i) Z1 J; b" D6 U& F- w# r8.10 Summary of Important Points.
9 W$ Q1 X  R9 S/ ~6 W( `8.11 Review Questions.
" L  K  n; Z, ?& m8.12 Brief Answers and Explanations.
) ?' m! C8 D4 Y# C# [( _. c; c8.13 Further Reading.  C3 X# u- `6 o7 B- @
9 GOOD MANUFACTURING PRACTICE: REGULATORY REQUIREMENT.  l! ]8 q. `3 d. b7 g' k+ n
9.1 Introduction.
, D- |+ ?" M! y9 Q3 B  _9.2 United States.. a% R8 r3 p1 G# E
9.3 Europe.3 E8 ?+ ~# h: S" w0 Q! U
9.4 International Conference on Harmonization.
7 a2 c$ \# Y: |8 t9.5 Core Elements of GMP.
: u- k& t( ]( g/ `, H9.6 Selected GMP Systems.5 p" ]* W6 [  g- s) Y. M
9.7 The FDA’s New cGMP Initiative.  g! P/ K+ }- r
9.8 Case Study #9.
# `2 \* K' E+ U7 `- j" f9.9 Summary of Important Points.
- {1 T, Z+ @  t3 p# Q' G, N9.10 Review Questions.5 r* f5 `8 |7 |+ J3 n
9.11 Brief Answers and Explanations.$ B3 w0 ~, H3 V. U& c& Q' w, z
9.12 Further Reading.
8 {; \/ G0 X" `, y5 {3 B10 GOOD MANUFACTURING PRACTICE: DRUG MANUFACTURING.
% Y7 G+ @" `. e10.1 Introduction.
" f' Q8 L8 t. p% ^" h) E, b+ n5 E10.2 GMP Manufacturing.
8 T- i) J: p" B. s6 c5 Y( _( C10.3 GMP Inspection.7 b( @. t& w2 ?% t8 J
10.4 Manufacture of Small Molecule APIs (Chemical Synthesis Methods).$ E. O2 {  f8 Q$ e
10.5 Manufacture of Large Molecule APIs (Recombirant DNA Methods).1 n- `3 L( P) \
10.6 Finished Dosage Forms.( c5 H5 `7 \6 S, X# v  Q: Z1 }3 N
11 FUTURE PERSPECTIVES.
9 R0 u9 e. j% ]4 {% H4 e) N7 z11.1 Past Advances and Future Challenges." f6 {' S5 B6 X
11.2 Small Molecule Pharmaceutical Drugs.' b9 z# u. |1 {3 ~, \) O6 a
11.3 Large Molecule Biopharmaceutical Drugs.
, X0 X3 _2 y& D# R11.4 Traditional Medicine.
& p* R) U6 F3 S11.5 Individualized Medicine.% r( a! j5 R4 h
APPENDIX 1 HISTORY OF DRUG DISCOVERY AND DEVELOPMENT.
3 B, W& q& R5 ]6 UA1.1 Early History of Medicine.
* z% p) M( w1 e  XA1.2 Drug Discovery and Development in the Middle Ages.
' G& t$ Z- F+ L. GA1.3 Foundation of Current Drug Discovery and Development.1 C# e' Q$ M3 L
A1.4 Beginnings of Modern Pharmaceutical Industry.
4 m" B9 F" P5 e0 U, X- H/ T4 RA1.5 Evolution of Drug Products.4 h! M: Q  F8 m# Z. y8 t# M, {
A1.6 Further Reading.
4 o3 ~& t$ U2 HAPPENDIX 2 CELLS, NUCLEIC ACIDS, GENES, AND PROTEINS.
" z0 V% y- S( h* |/ v1 U7 H; W; xA2.1 Cells.& y6 f9 b! B6 J; c( C
A2.2 Nucleic Acids.
, D1 A- U5 b" }; [A2.3 Genes and Proteins.
% J6 w+ `5 L3 k: j) NA2.4 Further Reading.( |' L( T% v4 B- A: M
APPENDIX 3 SELECTED DRUGS AND THEIR MECHANISMS OF ACTION.
/ Q3 e4 ~, j) ]- mAPPENDIX 4 A DHFR PLASMID VECTOR.
0 C  O1 ]- v! u- Q2 qAPPENDIX 5 VACCINE PRODUCTION METHODS.; C/ |8 F  j/ @; w6 D
APPENDIX 6 PHARMACOLOGY/ TOXICOLOGY.
, b) C: \! h' PREVIEW FORMAT.
; V4 E: ~; \- W& h- j7 `: jAPPENDIX 7 EXAMPLES OF GENERAL BIOMARKERS.7 r* n3 f: t4 Y0 V3 t
APPENDIX 8 TOXICITY GRADING.
# A% p$ f; ?, l* k: ^4 UAPPENDIX 9 HEALTH SYSTEMS IN SELECTED COUNTRIES.. e: B0 D, @9 `/ Z9 e" B% k7 T& T7 c2 U- N
ACRONYMS.
8 G- t( g# @9 b# B/ oGLOSSARY.& _( ?$ {0 V6 s  t& [. d6 A- p& H
INDEX.2 H) n6 n) ~( _3 q9 @  }
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