Book Review

of drug pharmacokinetics and pharmacodynamics, particularly for drug-drug interaction. A dedicated chapter for mice models with conditional gene mutations (inducible transgenes and conditional gene inactivation) discusses the advantages of this model over knockout and knockin systems and its applicability in drug development. The tetracycline-inducible promoter and Cre/lox models are used to illustrate to the reader the clinical application of this system. The Analytical Laboratory Techniques section outlines the basics of LC/MS/MS methodology as well as its use in the pharmacokinetic analysis of newer agents and their metabolites. Another section is dedicated to Delivery Systems: liposome formation, polymer drug conjugates, and pro-drug development are dedicated separate chapters. Several helpful examples are listed for these delivery systems, which help illustrate the advantages and disadvantages of each system. These sections are a bit technical for the clinician but do provide some basic background information. The Clinical Studies and Specifi c Issues in Drug Development sections of this book comprise an excellent introduction on clinical drug development for basic and clinical researchers alike. These sections are comprehensive and include an excellent chapter on phase I clinical trial design. This chapter covers dosing transition from animal models to humans and various subsequent modes of escalation: standard escalation, continual reassessment method, accelerated titration design, and pharmacokinetic guided-dose escalation. The advantages of accelerated titration over standard escalation in terms of the earlier identifi cation of the maximum tolerated dose and the requirement of a smaller number of patients are pointed out. Special topics such as clinical trials in pediatric and elderly populations, vaccine studies, and quality of life measurement are discussed. The book emphasizes the need to assess surrogate markers of biological activity, from PET scans to enzymatic/target inhibition, as part of phase I studies. The importance of integrating pharmacogenomics in drug development is emphasized through a thorough discussion of TPMT and DPD defi ciencies and UGT1A1 polymorphisms in the respective settings of 6-MP, 5-FU, and irinotecan administration. To conclude, this handbook covers adequately various aspects of drug development, from drug discovery to licensing. The clinical section would be highly recommended for medical residents or researchers with interest in clinical research. Similarly, the drug discovery preclinical analytical sections provide a nice introduction to the ‘bench world of drug discovery’ for those on the clinical side of drug development. Marwan G. Fakih, Buffalo, N.Y. Donald L. Trump, Buffalo, N.Y. D.R. Budman, A.H. Calvert, E.K. Rowenski (eds.)