Atnaujinkite slapukų nuostatas

Pharmacokinetics: Processes, Mathematics and Applications 2nd Revised edition [Kietas viršelis]

  • Formatas: Hardback, 400 pages, aukštis x plotis: 152x229 mm, weight: 907 g
  • Serija: ACS Professional Reference Books
  • Išleidimo metai: 01-Aug-1997
  • Leidėjas: American Chemical Society
  • ISBN-10: 0841234817
  • ISBN-13: 9780841234819
Kitos knygos pagal šią temą:
  • Formatas: Hardback, 400 pages, aukštis x plotis: 152x229 mm, weight: 907 g
  • Serija: ACS Professional Reference Books
  • Išleidimo metai: 01-Aug-1997
  • Leidėjas: American Chemical Society
  • ISBN-10: 0841234817
  • ISBN-13: 9780841234819
Kitos knygos pagal šią temą:
Revised to reflected changes in pharmacokinetics and drug metabolism since the first edition of 1986, this book provides new material on drug transport and drug disposition in patients with hepatic or renal function impairment. A new section on the applications of pharmacokinetics and drug metabolism in drug discovery and development offers a critical comparison of pharmacokinetics and toxicokinetics as contributing disciplines in drug development. Annotation c. by Book News, Inc., Portland, Or.

Pharmacokinetics is the study of the absorption, distribution, metabolism, and excretion of drugs in humans. This book, written by an internationally known researcher, teaches the basic principles, including drug transport, parenteral and enteral routes of drug administration, and factors affecting drug absorption, distribution, and metabolism. Extensively revised, this edition presents the mathematics of pharmacokinetics with various single- and multi-compartment models including detailed descriptions of metabolite and nonlinear pharmacokinetics. It also describes renal and hepatic drug clearance, and the influence of kidney and liver impairment on these functions. Taking a tutorial approach throughout, the author provides both a clear introduction to pharmacokinetics and a critical look at how this science affects drug discovery and development.
Preface xiii
DRUG ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION 1(198)
1. Drug Absorption, Distribution, Metabolism, and Excretion
3(8)
Different Approaches to Pharmacokinetics
4(5)
References
9(2)
2. Drug Transport
11(8)
The Cell Membrane
11(1)
Membrane Transport
12(5)
Summary
17(1)
References
17(2)
3. Parenteral Routes of Drug Administration
19(24)
Intraarterial Administration
20(1)
Intrathecal Administration
20(1)
Intravenous Administration
21(2)
Intramuscular Administration
23(1)
Buccal Administration
24(1)
Intranasal Administration
25(3)
Inhalation
28(3)
Transdermal Administration
31(6)
Vaginal Administration
37(1)
Rectal Administration
38(1)
Summary
39(1)
References
40(3)
4. Enteral Routes of Drug Administration
43(20)
Physiology of the GI Tract
43(2)
GI Structure and Motility Factors
45(5)
Gastrointestinal Blood Flow in Relation to Drug Absorption
50(1)
Special Transport Mechanisms
51(1)
Animal Models for Oral Drug Absorption
52(7)
Summary
59(1)
References
60(3)
5. Factors Influencing Absorption and Bioavailability After Enteral Administration
63(12)
Metabolism in the Gut
64(1)
Metabolism in the Lung
65(1)
Hepatic Metabolism and the First-Pass Effect
66(3)
Enterohepatic Circulation
69(2)
Factors Influencing the First-Pass Effect
71(2)
Summary
73(1)
Problems
73(1)
References
73(2)
6. Physicochemical and Formulation Factors Affecting Drug Absorption
75(20)
Chemical Factors
75(1)
Physical Factors
76(2)
Formulation Factors
78(2)
In Vitro-In Vivo Correlations
80(1)
Excipients
81(1)
Coated Tablets
82(1)
Controlled-Release Formulations
82(7)
Absorption Enhancers
89(4)
Summary
93(1)
References
93(2)
7. Clinical Factors and Interactions Affecting Drug Absorption
95(24)
Influence of GI Disease on Drug Absorption
95(5)
Drug-Drug Interaction Affecting Absorption
100(5)
Drug-Food Interactions Affecting Absorption
105(11)
Conclusions
116(1)
Summary
116(1)
References
117(2)
8. Drug Distribution
119(26)
Distribution-Concentration Relationships
120(1)
Capillary Permeability
121(1)
Perfusion and Diffusion Effects
122(2)
Binding of Drugs to Tissues
124(4)
Intravascular and Extravascular Drug Binding
128(7)
Penetration of Drug into the Central Nervous System
135(4)
Methods of Determining Drug Distribution
139(2)
Summary
141(1)
Problems
142(1)
References
142(3)
9. Drug Metabolism
145(18)
Sites of Drug Metabolism
145(2)
Mechanisms of Drug Metabolism
147(9)
Species, Sex, and Age Differences
156(3)
Steric Factors
159(1)
Enzyme Induction
159(1)
Enzyme Inhibition
160(1)
Summary
160(1)
References
161(2)
10. Effect of Liver Disease on Drug Metabolism and Pharmacokinetics
163(12)
Function and Structure of the Liver
164(1)
Types and Severity of Liver Disease
164(1)
Effects on Pharmacodynamics and Pharmacokinetics
165(4)
Examples of Effects of Liver Disease on the Pharmacokinetics of Some Drug Classes
169(2)
Conclusions
171(1)
Summary
172(1)
References
172(3)
11. Renal Excretion
175(12)
Structure and Function of the Kidney
175(3)
Clearance
178(1)
Renal Clearance and Plasma Clearance
179(3)
Relationship Among Clearance, Drug Elimination Rate, and Half-Life
182(2)
Summary
184(1)
Problems
184(1)
References
185(2)
12. Drug Elimination in Renal Impairment
187(12)
Methods of Measuring Renal Function
188(2)
Use of Creatinine Clearance to Predict the Effect of Renal Impairment on Drug Elimination
190(1)
Methods of Dosage Adjustment
191(3)
Maintenance of Patients with End-Stage Kidney Disease
194(1)
Summary
195(1)
Problems
196(1)
References
197(2)
THE MATHEMATICS OF PHARMACOKINETICS 199(124)
13. The One-Compartment Open Model with Intravenous Dosage
201(22)
The One-Compartment Open Model with Bolus Intravenous Injection
202(5)
The Trapezoidal Rule
207(3)
Urinary Excretion Kinetics
210(1)
Construction of Sigma-Minus Plots
211(2)
Zero-Order Drug Input and First-Order Elimination
213(6)
Summary
219(1)
Problems
219(2)
References
221(2)
14. The One-Compartment Open Model with First-Order Absorption and Elimination
223(22)
General Aspects of First-Order Absorption and Elimination
223(3)
Graphical Estimation of Parameters
226(4)
Other Parameters Associated with First-Order Absorption and Elimination
230(2)
Drug Absorption Plots
232(2)
Area Under the Drug-Concentration Curve (AUC)
234(2)
Absorption Lag Time
236(1)
Cumulative Urinary Excretion of Unchanged Drug
237(4)
Summary
241(1)
Problems
242(1)
References
243(2)
15. Multiple-Dose Kinetics
245(14)
Drug Accumulation with Repeated Doses
245(5)
Drug Accumulation Rate
250(2)
The Degree of Drug Accumulation with Repeated Dosing and the Loading Dose Required To Instantaneously Achieve Steady-State Levels
252(1)
First-Order Absorption Case
253(3)
Summary
256(1)
Problems
256(1)
References
257(2)
16. Metabolite Pharmacokinetics
259(12)
Pharmacokinetics of Metabolite Formation and Elimination
259(3)
Analysis of Metabolite Concentrations in Plasma, and Urinary Excretion
262(3)
Resolving the Pharmacokinetics of Metabolite and Parent Drug
265(3)
Summary
268(1)
Problems
268(1)
References
269(2)
17. The Two-Compartment Open Model with Intravenous or Oral Administration
271(26)
The Two-Compartment Model with Bolus Intravenous Injection
272(1)
Interpretation of Drug-Concentration Profiles in Plasma To Obtain Parameter Estimates
273(3)
Graphical Estimation of Kinetic Parameters
276(2)
Derivation of AUC(0XXX), Plasma Clearance, and Renal Clearance
278(1)
Volume of Distribution at Equilibrium
279(3)
Kinetics of Tissue Distribution
282(1)
Obtaining Parameter Estimates from Urinary Excretion Data
283(2)
The Two-Compartment Model with First-Order Drug Input
285(3)
Drug Concentration in the First Compartment
288(4)
Some Model-Independent Parameters for a Drug that Obeys Two-Compartment Model Kinetics
292(2)
Summary
294(1)
Problems
295(1)
References
295(2)
18. Physiological Pharmacokinetic Models
297(14)
Description of Physiological Pharmacokinetic Model
297(2)
Organ Clearance
299(1)
Blood Flow Rate-Limited Transport
300(5)
Membrane-Limited Transport
305(1)
Experimental Considerations
306(2)
Summary
308(1)
Problems
309(1)
References
309(2)
19. Nonlinear Pharmacokinetics
311(12)
Saturable Processes
311(2)
Expressions Useful in Elimination Kinetics
313(3)
Obtaining Estimates of V(m) and K(m) from Plasma-Level Data
316(2)
Influence of Saturable Kinetics on Drug Elimination, Area Under the Drug-Concentration Curve, and First-Pass Effect
318(3)
Summary
321(1)
Problems
321(1)
References
322(1)
APPLICATIONS OF PHARMACOKINETICS IN DRUG DISCOVERY AND DEVELOPMENT 323(32)
20. Pharmacokinetics and Toxicokinetics
325(6)
Pharmacokinetics and Pharmacodynamics
325(1)
Toxicokinetics and Toxicodynamics
326(1)
Technical Differences Between Pharmacokinetics and Toxicokinetics
326(2)
Philosophical Differences Between Pharmacokinetics and Toxicokinetics
328(1)
Conclusions
329(1)
Summary
329(1)
References
329(2)
21. Role of Pharmacokinetics in Drug Discovery and Development
331(12)
Regulatory Submissions
331(1)
Drug Discovery and Development
332(8)
Regulatory Submissions and Drug Labeling
340(1)
Postsubmission and Postmarketing Studies
341(1)
Conclusions
341(1)
Summary
342(1)
References
342(1)
22. Integration of Pharmacokinetics into Research and Development
343(12)
The R&D Sequence
343(1)
Statement of the Problem
344(1)
The Alternatives
344(1)
Comparison of the Alternatives
345(5)
Conclusions
350(2)
Summary
352(1)
Reference
353(2)
APPENDIXES 355(26)
Appendix I: Computer Methods and Software for Pharmacokinetic Data Analysis 357(2)
Appendix II: Worked Answers to Problem Sets 359(14)
Appendix III: Nomenclature 373(4)
Appendix IV: Glossary 377(4)
INDEX 381