Abstract
This is a book I would like to have on my shelf. Paging through it reminded me of the old days of browsing through the family encyclopedia. There are lots of entries that catch one’s attention, and I found many old acquaintances.
The brief preface to the ninth edition describes the addition of 280 entries, a 30% increase over the previous edition. The target audience, although not directly named, seems to be forensic and analytical toxicologists or those who might need access to basic dispositional information on a drug or toxicant, including a summary of analytical methodology and citations.
This edition is graced, for the first time, with a prologue by Robert J. Flanagan titled “Guidelines for the Interpretation of Analytical Toxicology Results,” a reasonable treatise on considerations in collection, reporting, and interpretation of quantitative toxicological information. The guidelines appear to be directed to the interpreter of quantitative toxicant information. In this regard, pharmacokinetics (PK) and dispositional information in the individual monographs might be helpful for context. A useful addition to this section would have been a brief review of newer methodology for quantitative analysis, such as ultra performance liquid chromatography and high-resolution mass spectrometric techniques such as multiple mass defect filtering. These would appear to lend a high degree of improved sensitivity and specificity to toxicological methodology.
The body of the book is composed of about 950 or so monographs; the exact number is not clear, but they take up 1845 pages. Each entry is about 1 to 3 pages, and most show the structure, 4 or 5 basic PK parameters (half-life, volume of distribution, fraction bound, blood/plasma ratio). Sometimes the originator is listed (eg, drug company), but mostly not. It would be nice to include molecular weight and perhaps a few other physicochemical parameters. The entries are listed alphabetically by name (generic name for drugs, which appear to be the United States Adopted Names designation, but this is not clear from the preface or other parts of the book). For most compounds, especially drugs, the monograph is conveniently ordered in the form Occurrence and Usage, Blood Concentration, Metabolism and Excretion, Toxicity, and Analysis. Each section is a few sentences of informative description supported by citations. The latter is a key part of the value of this book. Although one can readily search PubMed (a service not available for the earliest editions of the book), having a handful of citations is always a great way to begin a more detailed search online.
I didn’t read every word in the book. But I did turn every page: selenium has 3.5 pages of text; mercury has 4.2 pages. Phenytoin has 3.5 pages. Nicotine has 4 pages (including citations), as does morphine. Methadone has almost 5 pages. Cocaine has 5 pages. The trend seemed to be toward more pages for addictive drugs and toxic metals.
Indexing and cross-referencing of entries is very limited. The index lists various drug classes, but entries are shown only by page number, not by name. Similarly, some entries refer to related drugs or chemicals but only by name, not page number (although since entries are arranged alphabetically, it would be simple to find by that means). Parecoxib, a prodrug of valdecoxib, has a 1.5-page entry. Although valdecoxib is (or was) a marketed drug, there is no entry for it, nor is it or its trade name (Bextra) listed in the index. The limited degree of cross-referencing might be a considerable deficiency for some readers who would like to quickly refer to related drugs or chemicals. That said, it’s likely that many users need to find information on only a single drug or chemical and can do so by simply finding the compound in the alphabetical order of the book.
Although mechanisms of metabolism are occasionally mentioned, there are very few (if any) references to interactions with drug transporters. For instance, the entry for digoxin notes that the nonlinear PK observed with coadministered quinidine is probably due to reduction in digoxin binding to skeletal muscle (p 507) but, in fact, the nonlinear PK is now thought to be caused by inhibition of gut P-glycoprotein. 1 For cyclosporin, no transporter function was noted, even though this is an important and well-known component of the disposition and drug-drug interactions associated with cyclosporin. Although the author could not be expected to provide meticulous updates to all entries, this is one area where “crowd sourcing” (ie, user-supplied updates or edits, as done with Wikipedia) would result in a more contemporary and possibly more accurate entry.
I did a quick, though unfair, comparison to Wikipedia. Propiomazine was found in Wikipedia. Although the latter entry lacked the 7 citations or metabolic path shown in the book, it included the MW and structure that could be easily copied or imported. It also included hyperlinks to related information such as antihistamines (including H1, H2, H3, and H4 classes of latter). A random selection of other entries showed all were covered in Wikipedia but often with less complete information. For amisulpride, Wikipedia showed much more basic chemical information; however, the book provided considerably more detail on the toxicity of amisulpride, referencing at least 10 publications, including several published in the past 5 years. The book entry for propofol noted the newly described toxicity associated with the drug, known as “propofol infusion syndrome,” citing articles published in 2009 and 2010. The pop star Michael Jackson died from a propofol overdose, an observation that was covered in the Wikipedia article and supported with references.
The criteria by which compounds are included or excluded from the book are not clear. The author might be forgiven for not including 2 antiviral therapeutics approved in 2011 (telaprevir and boceprevir); however, an important and widely discussed new antiplatelet drug, prasugrel, was not included, even though it was approved in the United States and European Union in 2009 and might be considered a successor to clopidogrel (which is included in the current edition). Although borate was covered as a toxicant, the anticancer drug bortezimib (first synthesized in 1995 and approved in the United States in 2003) was not. It might be nice if there were a Web site where users could post proposed additions and updates to the current edition. This would lessen the burden on the author for literature surveillance and ready source of material to be curated for the next edition.
This is a densely informative book—limited in depth but broad in scope. The chemical structures and a thumbnail sketch of the metabolism and toxicity are good anchors. Sometimes this might be sufficient information for a reader, or it might provide a few key citations that would help find the detailed information needed on metabolism, toxicity, or analysis of a drug. However, any subsequent investigation would almost certainly begin with a Web browser and would usually quickly lead to a more comprehensive display of information than that found in the book. In this regard, the analogy to the old encyclopedia brings to mind the anachronistic nature of this volume—a reference text published in print and fixed in time. Although I’d like to have this book on my shelf, that is where it would probably spend most of its life—nearby if I happened to be at my desk and was willing to heft the volume to the desktop but otherwise poorly accessible in an age where we expect most reference needs to be a few keystrokes away. Nevertheless, I suspect many users of this text are familiar with this format and use it as a handy nearby reference. In this manner, the updated version would provide added value. Perhaps the next edition might include a companion electronic version, with periodic updates and a path for users to submit edits or additional entries.