Quinolone Antimicrobial Agents

BOOK REVIEWS Chemiluminescence: Principles and Applications in Biology and Medicine. By A. K. Campbell. Ellis Horwood: ChiChester, UK. 1988.608 pp. 17 x 25 cm. ISBN 0-89573-501-6. $196.00.

This book from the Ellis Horwood Series in Biomedicine covers a broad spectrum of topics in chemiluminescence and bioluminescence, which the author defines as visible chemiluminescence from living organisms. Chapter 1is devoted to the history of chemiluminescence and introductory principles for the study of chemiluminescence. The remainder of the book includes a detailed presentation of the physics, biology, and chemistry of chemiluminescence, and a basic presentation of the applications for chemiluminescent assay systems. Chapter 2 covers detection and quantification of chemiluminescence with special emphasis on the physics of luminometry and the design of luminometer instrumentation. Chapter 3 is a superb presentation of the biology and biochemistry of bioluminescence, and is particularly noteworthy for its approach to the study of “living light”. The author includes a list of luminous species in Appeindix 11. Chapter 4-7 are extensive in their multi-disciplinary approach to chemiluminescent assay systems, which are presented in the context of “the need for chemiluminescence analysis in biology, medicine, and biotechnology”. These chapters focus on the chemistry, biology, and physics of the most widely studied chemiluminescent systems of enzymes and metabolites, oxygen and its metabolites, photoproteins and inorganic ions, and ultraweak “cellular” chemiluminescence. Chapter 8 deals with applications of chemiluminescent immunoassays and chemiluminescent DNA probe assays. Practical applications of chemiluminescent immunoassays a r e presented in the context of a n alternative technology to RIA and other immunoassay methods. The discussion of chemiluminescent DNA probe technology is mostly theoretical without the benefit of recent data €or this application. Chapter 9 is a n advanced technical discussion of chemiluminescence energy transfer with emphasis on physical chemistry and thermodynamics. This book provides a review of chemiluminescence and bioluminescence that is rernarkable for the range of information presented. The book is highly technical for most topics and is best suited for readers who are well versed in the field. However, readers interested in a basic understanding of bioluminescence in nature will find the pertinent sections of this book enjoyable to read and informative. At the end of each chapter the author has included a recommended reading list that is extensive and well suited for different levels of interest. References are altio provided for a variety of specific applications that are listeld but not described in any detail. This book is timely and highly recommended for individuals interested in the development of chemiluminescence applications in science and clinical medicine.

toxicology of ciprofloxacin, and summarizes human clinical studies performed during the premarketing period. The text is similar to that provided in the investigator’s brochure and is consistent with FDA approved labeling for ciprofloxacin. The first two sections describe the chemistry and assay of ciprofloxacin. Chemical characteristics of ciprofloxacin are described, but there is no discussion of strudursactivity relationships. The descriptions of assay procedures are brief and incomplete. However, references are provided for those wishing to carry out analysis of ciprofloxacin by HPLC or microbiological assay. The section describing the mechanism of action and resistance is well written and easy to understand. The fourth section deals with the pharmacokinetics and tissue penetration of ciprofloxacin. The book implies that the bioavailability of ciprofloxacin is dose independent. However, several of the cited studies suggest a decreasing fraction of dose absorbed with increasing dose. Clearance and volume of distribution are reported assuming 100 percent bioavailability. Information on hemodialysis removal of ciprofloxacin is misleading. The cited study compared only half-life on and off hemodialysis without attention to the percent of total body stores removed. Studies with other fluoroquinolones demonstrate decreased half-life on dialysis, post-dialysis rebound of serum concentrations, and poor recovery in dialysate fluid. Most of the information on animal toxicology is unpublished previously, and is therefore of great value. Data on the in vitro activity of ciprofloxacin is extensive and very helpful. The seventh and largest section describes data from premarketing clinical studies. Unfortunately, there is no discussion of the most appropriate use of ciprofloxacin with respect to therapeutic and economic considerations, and alternative antimicrobials. The final three sections are titled “Safety and Tolerability”, “Dosage and Administration”, and “Prescribing Information”, respectively.The safety data summarizes adverse events noted in premarketing studies. Recommendations for dose in severe renal impairment (250 mg every 18 h) is impractical and will lead to error, especially in outpatient treatment. A recommendation of 500-750 mg every 24 h or 250 mg every 12 h would be more appropriate. The prescribing information is a duplicate of the FDA approved package insert. The book is a useful reference for those involved with the clinical use of ciprofloxacin. Most individuals however, will not be able to justify the price considering the limited scope of this book. David E. Nix Clinical Pharmacokinetics Laboratory Millard Fillmore Hospital Buffalo, NY 14209

Peter E. Andreotti South Florida Bioavailability Clinic Fort Lauderdale, FL 33334 Quinolone Antimicrobial Agents. Edited by John S. Wolfson and David C. Hooper. American Society for Microbiology: Washington, DC. 1989. 290 pp. 23 x 15 cm. ISBN 155581-007-1. $29.00 ASM member, $39.00 non-member. Ciprofloxacin Product Information Monograph: Compendium of Preclinical and Clinical Data. Marcel Dekker: New York. 1988. 160 pp. 15 x 23 cm. Price $35.00.

The book provides significant information on the chemistry, pharmacology, pharmacokinetics, microbiology, and animal 0022-3549/89/’0900-0787$0 1.00/0 0 1989, American Pharmaceutical Association

This is the second book which has been published on the fluoroquinolones. The introductory chapter is followed by a chapter on the mechanisms of action and resistance to quinolone antimicrobial agents by Wolfson, Hooper, and Swartz. The current thinking on the mechanism by which the Journal of Pharmaceutical Sciences i 787 Vol. 78,No. 9,September 1989

fluoroquinolones inhibit DNA gyrase and stop bacterial cell growth with resulting cell death is discussed. The complex nature of this interaction is clearly presented followed by a detailed discussion of the mechanisms of bacterial resistance to the quinolones. The excellent in vitro activity of the quinolones against a wide variety of bacteria relative to the older quionolones, such as nalidixic acid, is described by Eliopoulos and Eliopoulos. Compound S-25932is mentioned as closely related to S-25930 without any description of the structure. Temafloxacin is incorrectly described as possibly having clinically useful activity against anaerobic bacteria. Tosufloxacin (T-3262, A-60969) has significant activity against anaerobes but is not described. Fadors which affect the in vitro activity of the fluoroquinolones,such as pH, urine, and divalent cations, are adequately reviewed. Drusano deals with the pharmacokinetics of the quinolones in humans. The pharmacokinetics in laboratory animals are not described. The compounds are differentiated by whether they are excreted by the renal route, by the bile route, or by both the kidneys and liver. The need to alter the dose in cases of renal and liver dysfunction is discussed. The efficacy of the fluoroquinolones in the treatment of a variety of infectious diseases is described in Chapters 5-13. The experience of infectious disease specialists should serve as a useful guide for those practicing clinical medicine. The limited experience in treating endocarditis and meningitis is supplemented by description of results obtained from treating experimental animal infections. For all the clinical indications, the fluoroquinolones offer the advantage of oral treatment of infections, which in the past could only be treated with parenteral antibiotics. Their limitation is their weaker activity against gram-positive bacteria relative to enteric bacteria and Pseudomonas aeruginosa. The adverse effects of the quinolones are described by Woolfson and Hooper. The low frequency of side effects with the fluoroquinolones shows that these compounds are generally safe and their adverse effect profiles compare favorably with those of other classes of antibacterial agents. The potential for mutagenicity and interaction with other drugs are described in this chapter. The overview and conclusions are presented in the last chapter by Moellering. The fluoroquinoloneswhich have been approved for human use either in the United States or Europe are adequately describedin this book. There is no discussion of structure-activity relationships or the chemical structures and properties of many compounds now in early development. Therefore, this book will be useful to medical microbiologists and infectious disease specialists but less useful to the pharmaceutical scientist. Prabhavathi B. Fernandes Department of Microbial Genetics and Biochemistry The Squibb Institute for Medical Research

Princeton, NJ 08543-4000

Mass Spectra of Prostaglandins and Related Products. By Cecil Robert Pace-Asciak. (Volume 18 in Advances in Prostaglandin, Thromboxane and Leukotriene Research, edited by B. Samuelsson and R. Paoletti). Raven Press: New York. 1989. 565 pp. ISBN 0-88167-474-5. $98.00. This book is a compendium of 750 mass spectra of prostaglandins and related oxygenated eicosanoids. The

788 1 Journal of Pharmaceutical Sciences

Vol. 78, No. 9, September 1989

comprehensive coverage includes the precursor fatty acids, hydrogenated fatty acids, lipoxygenase products of fatty acids, prostaglandins, thromboxanes, leukotrienes, cyclic ether fatty acids, and metabolites of prostaglandins, thromboxanes, and leukotrienes. Additional chapters describe the biosynthetic and catabolic pathways of prostaglandins and related products, and methods useful in derivatizing products for GC-MS analysis. The author, who is an experienced researcher in the area, wrote the book to enable researchers to directly verify the identity of products extracted from biological sources and as an aide in the design of quantitative assays using the selected ion monitoring technique. Chapter I describes the pathways involved in the biosynthesis and metabolism of prostaglandins, oxygenated eicosanoids, and thromboxanes. The description is brief, but complete. The schemes, which are standard textbook figures, lack numbering systems, which makes them difficult to relate to the text, and there is some confusion as to the preferred spelling for eicosanoid. Another inconsistency is that for certain structural classes, suitable derivatization procedures and ionization techniques are mentioned, while for others they are not. Chapter I1 is the atlas of the mass spectra. Each spectrum is presented as m / z versus intensity line drawings. Occasionally, the abscissa and ordinate are labeled. Many are from the author’s unpublished library. Because they are often copied directly from the literature, some show fragmentation processes and labeled fragment ions and others do not. Likewise, only some structures are included. The spectra are compiled in an order consistent with the pathways described in Chapter I. A check of selected spectra suggests that the representations are accurate. Chapter 111is a brief description of derivatization reactions commonly employed with these classes of compounds. The descriptions are sufficiently complete to be useful, although few of the reactions are evaluated with respect to the nature, GC suitability, or sensitivity of the resulting mass spectra. The rest of the book consists of references (dated from 1966 to 1985), a table of abbreviations, a table of contents, and a glossary. All are adequate, although the latter two sections use terminology which limits their use to someone with a background in lipid chemistry. This book will be extremely useful to experienced researchers who use mass spectrometry to study the biotransformation of this important class of bioactive chemicals. To researchers interested in quantitating these acids, it will be less useful because almost no consideration is given to negative chemical ionization mass, the most practical analytical technique for these very potent (low concentration) agents. Because the book contains no evaluation of the spectra, the derivatization procedures, the instrumentation, the ionization techniques, or the sensitivity of the observed response, researchers unfamiliar with either mass spectrometry or polyunsaturated lipid chemistry will not find it useful. Future compendia of this type will almost certainly be published in a floppy disc format, instead of the traditional book format used here. William A. Garland Department of Drug Metabolism Hoffmann-La Roche, Inc. Nutley, NJ 07110