Pharmacokinetics and Metabolism in Drug Design
Dennis A. Smith, Charlotte Allerton, Amit S. Kalgutkar, Han van de Waterbeemd, Don K. Walker
John Wiley & Sons, May 14, 2012 - Medical - 268 pages
In this new edition of a bestseller, all the contents have been brought upto-date by addressing current standards and best practices in the assessment and prediction of ADMET properties. Although the previous chapter layout has been retained, substantial revisions have been made, with new topics such as pro-drugs, active metabolites and transporters covered in detail in a manner useful to the Drug Discovery scientist. The authors discuss the parameters and processes important for the absorption, distribution and retention of drug compounds in the body, plus the potential problems created by their transformation into toxic byproducts.
While aimed at all those dealing professionally with the development and application of pharmaceutical substances, the readily comprehensible style makes this book equally suitable for students of pharmacy and related subjects. Uniquely comprehensive, the book relates physicochemistry and chemical structure to pharmacokinetic properties and ultimately drug efficacy and safety.
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absorption acid active ADME affinity agents allometric amine antagonists aqueous basic binding blood body bonding cells changes Chemical clearance clinical compared compounds concentration correlation depends described differences discovery Disposition dose Drug Metabolism effects enzyme example factor Figure formation function half-life hepatic human illustrated important increase inhibition inhibitor interactions intrinsic involved ionized Journal lead lipophilicity liver logD major measured mechanism Medicinal Chemistry membrane metabolite methods molecular molecules oral organic oxidation P-glycoprotein partition permeability Pharmaceutical pharmacokinetic Pharmacology phase plasma potency potential prediction present properties proteins range reactions reactive receptor relationship relatively renal Research scaling Sciences selectivity shown silico similar Smith solubility species structure studies substrate Table tissue toxicity Toxicology transporter unbound values vitro volume of distribution weight