Appendix II

### INTRODUCTION

This appendix provides a summary of basic pharmacokinetic information pertaining to drugs that are in common clinical use and are delivered to the systemic circulation by parenteral or non-parenteral administration. Because of space limitations, this list cannot be exhaustive. Drugs designed exclusively for topical administration and not to be significantly absorbed into the bloodstream (e.g., ophthalmic and some dermal applications; Chapters 64 and 65) are not included. A few other selection criteria have influenced the makeup of the list, but, in general, the authors have tried to include one or more representative drugs in each of the therapeutic areas in this text, based on distinct mechanism(s) of action. In some instances, drugs may be excluded because pharmacokinetics are not relevant to their therapeutic management. An obvious case is when drug efficacy is not apparently correlated with drug concentration in a reversible fashion (e.g., some cytotoxic anticancer drugs). Also, for a number of therapeutic antibodies, the antibody is administered at a fixed dose at prolonged intervals that allows for its near complete clearance (e.g., infliximab).

Often, the issue comes down to deciding which of the many drugs within a class should be selected. This is particularly problematic when the choices are largely therapeutic equivalents. Two criteria that have proven useful are prevalence of use and uniqueness of mechanism of action. For the present edition, we have consulted the "2008 Top 200 Branded Drugs by Total Prescriptions" and "2008 Top 200 Generic Drugs by Total Prescriptions" published in the respective May 22 and 26, 2009, issues of Drug Topics (http://drugtopics.modernmedicine.com) for usage data. Drugs that fall into the top 200 list are selected. As mentioned above, a less used drug may be included if it has a different mechanism of action than the frequently used drugs, some additional actions that offer a unique therapeutic advantage, or a more acceptable side-effects profile.

Pharmacokinetic data for many older drugs not included in this appendix can be found in earlier editions of this book.

A major objective of this appendix is to present pharmacokinetic data in a format that informs the clinician of the essential characteristics of drug disposition that form the basis of drug-dosage regimen design. Table AII–1 contains quantitative information about the absorption, distribution, and elimination of drugs; the effects of disease states on these processes; and the correlation of efficacy and toxicity with drug concentrations in blood/plasma. The general principles that underlie the design of appropriate maintenance dose and dosing interval (and, where appropriate, the loading dose) for the average patient are described in Chapter 2. Their application using the data in Table AII–1 for individualization of dosage regimens is presented here.

To use the data that are presented, one must understand clearance concepts and their application to drug-dosage regimens. One also must know average values of clearance as well as some measures of the extent and kinetics of drug absorption and ...

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