By I. Elber. University of Colorado, Denver.
Yohimbine purchase 5mg bisoprolol otc blood pressure chart according to age, 424t Triptorelin cheap bisoprolol 10 mg on line blood pressure medication makes me dizzy, 393-395 Tromethamine buy bisoprolol 5 mg online enrique heart attack, 366-368 Z Tropicamide order bisoprolol 10mg with visa pulse pressure decrease, 416t Zafirlukast, 180-182 Trospium, 230-231 Zaleplon, 317-318 Tuberculosis Zidovudine, 266-270, 268i directly observable therapy for, 276 Zileuton, 180-182 drug regimens for treating, 276-280 Ziprasidone, 331-332 Typical antipsychotics, 333-336 Zolmitriptan, 86-88 i refers to an illustration; t refers to a table. Professor and Executive Dean, South Carolina College of Pharmacy, The University of South Carolina, Columbia, Medical University of South Carolina, Charleston, South Carolina William J. Professor and Dean, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Jane M. The information presented herein reflects the opinions of the contributors and reviewers. Drug information and its applications are constantly evolving because of ongoing research and clinical experience and are often subject to professional judgment and interpretation by the practitioner and to the uniqueness of a clinical situation. However, the reader is advised that the publisher, author, contributors, editors, and reviewers cannot be responsible for the continued currency or accuracy of the information, for any errors or omissions, and/or for any consequences arising from the use of the information in the clinical setting. Acquisition Editor: Hal Pollard Managing/Development Editor: Dana Battaglia Production: Silverchair Science + Communications, Inc. Library of Congress Cataloging-in-Publication Data Concepts in clinical pharmacokinetics / Joseph T. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without written permission from the American Society of Health-System Pharmacists. Intravenous Bolus Administration, Multiple Drug Administration, and Steady-State Average Concentrations… 45 Lesson 5. Relationships of Pharmacokinetic Parameters and Intravenous Intermittent and Continuous Infusions… 59 Lesson 6. Pharmacokinetic Variation and Model-Independent Relationships… 139 Practice Set 3… 153 Lesson 12. Glossary… 217 Index… 219 Acknowledgments The authors are indebted to George Francisco, Kim Brouwer, Stan Greene, Cecily DiPiro, William H. Reynolds for their review and suggestions during the preparation of the first and second editions. The third and fourth editions reflect the suggestions of many individuals who used the manual and recommended improvements. The rigorous effort and valuable suggestions provided by Dana Battaglia for this edition are greatly appreciated. Preface to the Third Edition This programmed manual presents basic pharmacokinetic concepts and procedures that are useful in pharmacy, medicine, and other health professions. Although this text is not intended to create a practitioner fully competent in clinical pharmacokinetics, it will provide an orientation to the concepts involved. After completing this text, the reader should be prepared to begin learning the pharmacokinetic techniques for clinical situations. The reader should participate in structured educational settings, such as a formal clinical pharmacokinetics course or a clerkship under an experienced clinical practitioner, to develop clinical skills related to pharmacokinetics. Readers who want in-depth understanding of the derivations of pharmacokinetic equations should consult an appropriate text. In this third edition, the manual is divided into 15 lessons to allow progression on a typical semester schedule of 15 weeks. The first 11 lessons include pharmacokinetic and pharmacodynamic principles as well as an overview of biopharmaceutic principles. Each of these lessons begins with a list of educational objectives and concludes with a series of questions. Answers and feedback for incorrect responses have been provided for the short-answer questions. Lessons 12 through 15 present brief patient case studies with aminoglycosides, theophylline, vancomycin, digoxin, and phenytoin so the reader can practice the use of pharmacokinetic equations. This edition will be accompanied by a Web-based version that will provide lessons to parallel each of the lessons in the print version. The Web-based version will include dynamic figures and simulators, calculators for applying pharmacokinetic equations, links to important Web pages, and interactive capability for discussion questions. Although the print version may be used independently, we believe that concurrent use of both versions will enhance learning. Pruemer January 2002 Preface to the Fourth Edition Although the fourth edition of Concepts in Clinical Pharmacokinetics continues to provide basic pharmacokinetic concepts and procedures that are useful in pharmacy, medicine, and other health professions, this new edition has been revised to be, we anticipate, even more instructive and user- friendly for the reader. All of the chapters are revised, with many new clinical correlates and some new figures. All similar equations are cross-referenced throughout the book to allow the student to compare the various equations. A new appendix, Basic and Drug-Specific Pharmacokinetic Equations, summarizes and lists all equations needed to dose selected drugs (aminoglycoside, vancomycin, theophylline, digoxin, and phenytoin). In addition, more in-depth answers and feedback for incorrect responses are provided for the short-answer questions. All features are designated with specific design elements for easy navigation throughout the chapters. The American Society of Health-System Pharmacists is accredited by the Accreditation Council for Pharmacy Education as a provider for continuing pharmacy education. Identify factors that cause interpatient variability in drug disposition and drug response. Describe situations in which routine clinical pharmacokinetic monitoring would be advantageous. Use both one- and two-compartment models and list the assumptions made about drug distribution patterns in each. Represent graphically the typical natural log of plasma drug concentration versus time curve for a one-compartment model after an intravenous dose. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. The development of strong correlations between drug concentrations and their pharmacologic responses has enabled clinicians to apply pharmacokinetic principles to actual patient situations. Receptor sites of drugs are generally inaccessible to our observations or are widely distributed in the body, and therefore direct measurement of drug concentrations at these sites is not practical. For example, the receptor sites for digoxin are believed to be within the myocardium, and we cannot directly sample drug concentration in this tissue. However, we can measure drug concentration in the blood or plasma, urine, saliva, and other easily sampled fluids (Figure 1-1). Kinetic homogeneity describes the predictable relationship between plasma drug concentration and concentration at the receptor site (Figure 1-2). Changes in the plasma drug concentration reflect changes in drug concentrations in other tissues. As the concentration of drug in plasma increases, the concentration of drug in most tissues will increase proportionally. Similarly, if the plasma concentration of a drug is decreasing, the concentration in tissues will also decrease. Figure 1-3 is a simplified plot of the drug concentration versus time profile after an intravenous drug dose and illustrates the property of kinetic homogeneity.
Except as pro- section order 5 mg bisoprolol with mastercard blood pressure 6090, if a statement of the trans fat vided for in paragraph (f) of this sec- content is not required and purchase 10 mg bisoprolol mastercard pulse pressure blood pressure, as a result purchase bisoprolol 5mg hypertension 2008, tion generic bisoprolol 5mg otc pulse pressure less than 10, if cholesterol content is not re- not declared, the statement "Not a sig- quired and, as a result, not declared, nificant source of trans fat" shall be the statement "Not a significant placed at the bottom of the table of nu- source of cholesterol" shall be placed trient values. Insoluble gram" may be used as an alternative, fiber content shall be indented under or if the serving contains less than 0. Total carbohydrate content shall tains less than 1 gram, the statement be calculated by subtraction of the sum "Contains less than 1 gram" or "less of the crude protein, total fat, mois- than 1 gram" may be used as an alter- ture, and ash from the total weight of native, and if the serving contains less the food. Sugars shall be not required or, alternatively, the defined as the sum of all free mono- statement "Contains less than 1 gram" and disaccharides (such as glucose, or "less than 1 gram" may be used, and fructose, lactose, and sucrose). Except as provided for in para- serving contains less than 1 gram, the graph (f) of this section, if dietary fiber statement "Contains less then 1 gram" content is not required and as a result, or "less than 1 gram" may be used as not declared, the statement "Not a sig- an alternative, and if the serving con- nificant source of dietary fiber" shall tains less than 0. Soluble fiber in the food, sugar alcohol content shall content shall be indented under dietary be declared. In lieu of the term protein content by weight: The state- "sugar alcohol," the name of the spe- ment "not a significant source of pro- cific sugar alcohol (e. Other carbo- adjacent to the declaration of protein hydrates shall be defined as the dif- content. Protein content may be cal- ference between total carbohydrate and culated on the basis of the factor of 6. Other car- tion of Official Analytical Chemists), bohydrate content shall be indented 15th Ed. The (i) For purposes of declaration of per- protein digestibility-corrected amino cent of Daily Value as provided for in acid score shall be determined by paragraphs (d), (e), and (f) of this sec- methods given in sections 5. For foods rep- include vitamin A, vitamin C, calcium, resented or purported for infants, the and iron, in that order, and shall in- corrected amount of protein (grams) clude any of the other vitamins and per serving is equal to the actual minerals listed in paragraph (c)(8)(iv) amount of protein (grams) per serving of this section when they are added as multiplied by the relative protein qual- a nutrient supplement, or when a claim ity value. I (4–1–10 Edition) (A) Required or permitted in a stand- Vitamin D, 400 International Units ardized food (e. The declara- Biotin, 300 micrograms tion may also include any of the other Pantothenic acid, 10 milligrams Phosphorus, 1,000 milligrams vitamins and minerals listed in para- Iodine, 150 micrograms graph (c)(8)(iv) of this section when Magnesium, 400 milligrams they are naturally occurring in the Zinc, 15 milligrams food. The additional vitamins and min- Selenium, 70 micrograms erals shall be listed in the order estab- Copper, 2. Chromium, 120 micrograms Molybdenum, 75 micrograms (iii) The percentages for vitamins Chloride, 3,400 milligrams and minerals shall be expressed to the nearest 2-percent increment up to and (v) The following synonyms may be including the 10-percent level, the added in parentheses immediately fol- nearest 5-percent increment above 10 lowing the name of the nutrient or die- percent and up to and including the 50- tary component: percent level, and the nearest 10-per- Calories—Energy cent increment above the 50-percent Vitamin C—Ascorbic acid level. When de- cant source of l (listing the vitamins clared, the percentages shall be ex- or minerals omitted)" is placed at the pressed in the same increments as are bottom of the table of nutrient values. No 4 years of age as provided for in para- other information shall be highlighted. Such information shall include: (iii) Information required in para- (i) "Serving Size": A statement of graphs (d)(3), (d)(5), (d)(7), and (d)(8) of the serving size as specified in para- this section shall be in type size no graph (b)(7) of this section. Except for the (ii) "Servings Per Container": The heading "Nutrition Facts," the infor- number of servings per container, ex- mation required in paragraphs (d)(4), cept that this statement is not re- (d)(6), and (d)(9) of this section and all quired on single serving containers as other information contained within the defined in paragraph (b)(6) of this sec- nutrition label shall be in type size no tion or on other food containers when smaller than 6 point. When provided, this information is stated in the net the information described in paragraph quantity of contents declaration. I (4–1–10 Edition) (4) A subheading "Amount Per Serv- that the percent for protein may be ing" shall be separated from serving omitted as provided in paragraph (c)(7) size information by a bar as shown in of this section. The numerical value shall saturated fat" is declared, in a column be followed by the symbol for percent with total "Calories" at the top, fol- (i. The position of this column more than four vitamins and minerals heading shall allow for a list of nutri- are declared, they may be declared ent names and amounts as described in vertically with percentages listed paragraph (d)(7) of this section to be to under the column headed "% Daily the left of, and below, this column Value. Less than 2,400 mg 2,400 mg tion, shall be given in a column and Total carbohydrate...... The Daily Value column as provided in symbol "<" may be used in place of paragraph (d)(7)(ii) of this section, pro- "less than. This information may be pre- formation may be moved to the right sented horizontally as shown in para- and set off by a line that distinguishes graph (d)(12) of this section (i. The caloric conversion in- (11)(i) If the space beneath the infor- formation provided for in paragraph mation on vitamins and minerals is not (d)(10) of this section may be presented adequate to accommodate the informa- beneath either side or along the full tion required in paragraph (d)(9) of this length of the nutrition label. The caloric conver- presented in a tabular display as shown sion information provided for in para- below. I (4–1–10 Edition) (12) The following sample label illus- (13)(i) Nutrition labels on the outer trates the provisions of paragraph (d) label of packages of products that con- of this section. When such one nutrition label with the informa- dual labeling is provided, equal promi- tion in the second language following nence shall be given to both sets of val- that in English. Information shall be presented in a that are identical in both languages format consistent with paragraph (d) of need not be repeated (e. All required informa- (1) Following the subheading of tion must be included in both lan- "Amount Per Serving," there shall be guages. The additional quantitative for different units, total calories and information may state the total nutri- calories from fat (and calories from ent content of the product identified in saturated fat, when declared) shall be the second column or the nutrient listed in a column and indented as amounts added to the product as pack- specified in paragraph (d)(5) of this sec- aged for only those nutrients that are tion with quantitative amounts de- present in different amounts than the clared in columns aligned under the column headings set forth in paragraph amounts declared in the required quan- (e)(1) of this section. The footnote (3) Quantitative information by shall clearly identify which amounts weight required in paragraph (d)(7)(i) of are declared. Any subcomponents de- this section shall be specified for the clared shall be listed parenthetically form of the product as packaged and after principal components (e. Such in- (5) The following sample label illus- formation shall not be put in a sepa- trates the provisions of paragraph (e) rate column. I (4–1–10 Edition) (g) Compliance with this section monounsaturated fat, or potassium. The shall be determined as follows: nutrient content of the composite is at (1) A collection of primary containers least equal to 80 percent of the value or units of the same size, type, and for that nutrient declared on the label. Unless a particular method of under section 403(a) of the act if the analysis is specified in paragraph (c) of nutrient content of the composite is this section, composites shall be ana- greater than 20 percent in excess of the lyzed by appropriate methods as given value for that nutrient declared on the in the "Official Methods of Analysis of label. The availability of this (6) Reasonable excesses of a vitamin, incorporation by reference is given in mineral, protein, total carbohydrate, paragraph (c)(7) of this section. If any ingredient ciencies of calories, sugars, total fat, which contains a naturally occurring saturated fat, trans fat, cholesterol, or (indigenous) nutrient is added to a sodium under labeled amounts are ac- food, the total amount of such nutrient ceptable within current good manufac- in the final food product is subject to turing practice. The nutrient considered granted until the Center for content of the composite is at least Food Safety and Applied Nutrition has equal to the value for that nutrient de- agreed to all aspects of the data base in clared on the label. Approvals carbohydrate, polyunsaturated or will be in effect for a limited time, e. Approval requests shall be more separately packaged foods that submitted in accordance with the pro- are intended to be eaten individually visions of §10. Guid- and that are enclosed in an outer con- ance in the use of data bases may be tainer (e. I (4–1–10 Edition) the values of the characterizing nutri- (j) The following foods are exempt ents in the foods proposed to be in the from this section or are subject to spe- category meet the compliance criteria cial labeling requirements: set forth in paragraphs (g)(3) through (1)(i) Food offered for sale by a person (g)(6) of this section. Proposals for such who makes direct sales to consumers categories may be submitted in writing (e. Claims or other nu- small size is contained in a gift pack- trition information subject the food to age, the food need not be included in the provisions of this section. Where firms in the gift package, and: have been in business less than 2 years, (A) It is used in small quantities pri- reasonable estimates must indicate marily to enhance the appearance of that annual sales will not exceed the the gift package; or amounts specified. For foreign firms (B) It is included in the gift package that ship foods into the United States, as a free gift or promotional item.