Clinical Pharmacokinetics

Table of Contents: Rational use of drug concentration measurements / James P. McCormack Estimating creatinine clearance / Robert E. Pachorek Renal drug dosing concepts / Dean A. Van Loo and Thomas C. Dowling Medication dosing in overweight and obese patients / Brian L. Erstad Pharmacogenomic impacts on pharmacokinetics / Cheryl Cropp Drug dosing in pediatric patients / Milap C. Nahata and Vinita Pai Therapeutic drug monitoring in the geriatric patient / Susan W. Miller Aminoglycosides / John E. Murphy and Kathryn Matthias Antidepressants / Patrick R. Finley Antiepileptics / Jacquelyn L. Bainbridge, Pei Shieen Wong, and Felecia M. Hart Antirejection agents / Tony K.L. Kiang and Mary H.H. Ensom Carbamazepine / Jacquelyn L. Bainbridge, Pei Shieen Wong, and Felecia M. Hart Digoxin / Robert DiDomenico and Robert L. Page II Ethosuximide / Jacquelyn L. Bainbridge, William R. Garnett, Pei Shieen Wong, and Felecia M. Hart Unfractionated heparin, low molecular weight heparin, and fondaparinux / A.Joshua Roberts and William E. Dager Lidocaine / Toby Trujillo Lithium / Stanley W. Carson and Lisa W.Goldstone Phenobarbital / Kimberly B. Tallian and Douglas M. Anderson Phenytoin and fosphenytoin / Michael Winter Theophylline / Hanna Phan and John E. Murphy Valproic acid / Barry E. Gidal Vancomycin / Jeremiah J. Duby, Monica A. Donnelley, Chelsea L. Tasaka, and Brett H. Heintz Warfarin / Ann K. Wittkowsky Titlepage 2 Table of Contents 6 Preface 12 Contributors 14 Introduction - GENERAL PHARMACOKINETIC PRINCIPLES 18 Section 1 - BASIC CONCEPTS AND SPECIAL POPULATIONS 28 Ch 1 - RATIONAL USE OF DRUG CONCENTRATION MEASUREMENTS 30 EVALUATING THE NEED FOR A DRUG CONCENTRATION MEASUREMENT 30 APPROACHES TO DOSING WITH LIMITED NEED FOR DRUG CONCENTRATION MEASUREMENTS 33 CONCLUSION 34 Ch 2 - ESTIMATING CREATININE CLEARANCE 36 FACTORS AFFECTING ESTIMATES OF GLOMERULAR FILTRATION RATE 36 CREATININE ASSAY STANDARDIZATION 37 FORMULAS TO ESTIMATE CREATININE CLEARANCE IN ADULTS 38 BODY WEIGHT 41 LOW SERUM CREATININE IN ELDERLY OR UNDERWEIGHT PATIENTS 42 AMPUTATIONS 42 SPINAL CORD INJURY 43 CHRONIC RENAL INSUFFICIENCY 43 DIALYSIS 43 LIVER DISEASE 43 PEDIATRICS 43 PATIENTS WITH UNSTABLE RENAL FUNCTION 45 ESTIMATING TIME TO STEADY STATE SERUM CREATININE CONCENTRATION 45 CREATININE CLEARANCE ESTIMATION IN UNSTABLE RENAL FUNCTION 45 Ch 3 - RENAL DRUG DOSING CONCEPTS 50 CLINICAL ASSESSMENT OF KIDNEY FUNCTION 50 MECHANISMS OF DRUG CLEARANCE 51 NONRENAL MECHANISMS 53 VOLUME OF DISTRIBUTION 54 DRUG DOSING STRATEGIES FOR CKD PATIENTS 54 HEMODIALYSIS AND CONTINUOUS RENAL REPLACEMENT THERAPY 58 CONCLUSION 64 Ch 4 - MEDICATION DOSING IN OVERWEIGHT AND OBESE PATIENTS 68 OBTAINING AN ACCURATE WEIGHT 68 BODY COMPOSITION CHANGES ASSOCIATED WITH OBESITY 68 SIZE DESCRIPTORS 70 PHARMACOKINETIC CONSIDERATIONS 72 ORAL ABSORPTION 72 CONCEPT OF DOSE PROPORTIONALITY 75 RECOMMENDATIONS FOR DOSING MEDICATIONS IN OBESE PATIENTS 76 GENETIC AND GENOMIC CONSIDERATIONS 77 Ch 5 - THE ROLE OF PHARMACOGENOMICS IN PHARMACOKINETICS 82 INTRODUCTION 82 BASIC DEFINITIONS 82 HISTORY OF PHARMACOGENETICS AND PHARMACOGENOMICS 83 CYTOCHROME P450 ENZYMES AND SOLUTE CARRIER TRANSMEMBRANE PROTEINS 84 IMPACT OF THE BLOOD–BRAIN BARRIER 84 SPECIAL POPULATIONS 86 PHARMACOGENOMIC EXAMPLES IN THERAPEUTICS 87 SUMMARY 88 Ch 6 - DRUG DOSING IN PEDIATRIC PATIENTS 92 GENERAL PHARMACOKINETIC INFORMATION 93 DISTRIBUTION 96 ELIMINATION 96 METABOLISM 98 FACTORS INFLUENCING DRUG DISPOSITION 98 PHARMACOGENOMICS IN CHILDREN 103 Ch 7 - THERAPEUTIC DRUG MONITORING IN THE GERIATRIC PATIENT 110 PHYSIOLOGIC CHANGES 112 DRUG ELIMINATION 116 AGE-RELATED PHARMACODYNAMIC CHANGES INFLUENCING DRUG RESPONSE 117 SUMMARY OF CHANGES 120 Section 2 - SPECIFIC DRUGS AND DRUG CLASSES 148 Ch 8 - AMINOGLYCOSIDES 150 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 150 DOSAGE FORM AVAILABILITY 151 GENERAL PHARMACOKINETIC INFORMATION 153 DOSING STRATEGIES 156 THERAPEUTIC RANGES 162 THERAPEUTIC MONITORING 163 PHARMACODYNAMIC MONITORING 169 DRUG–DRUG INTERACTIONS 171 DRUG–DISEASE STATE OR CONDITION INTERACTIONS 171 PHARMACOGENOMIC IMPLICATIONS OF AMINOGLYCOSIDE USE 173 Ch 9 - ANTIDEPRESSANTS 182 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 183 DOSAGE FORM AVAILABILITY 183 GENERAL PHARMACOKINETIC INFORMATION 183 DOSING STRATEGIES 187 THERAPEUTIC RANGE 189 THERAPEUTIC MONITORING 192 FURTHER CONSIDERATIONS FOR SAMPLING 193 PHARMACODYNAMIC MONITORING 193 DRUG–DISEASE STATE OR CONDITION INTERACTIONS 193 Ch 10 - ANTIEPILEPTICS 200 FELBAMATE 200 GABAPENTIN 202 LAMOTRIGINE 203 TIAGABINE 206 TOPIRAMATE 206 LEVETIRACETAM 208 OXCARBAZEPINE 209 ZONISAMIDE 210 PREGABALIN 212 LACOSAMIDE 213 RUFINAMIDE 215 VIGABATRIN 216 EZOGABINE 217 CLOBAZAM 218 PERAMPANEL 220 ESLICARBAZEPINE 221 USE OF THE NEWER ANTIEPILEPTIC DRUGS 222 GENERIC SUBSTITUTION OF AEDS 223 Ch 11 - ANTIREJECTION AGENTS 232 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 233 GENERAL PHARMACOKINETIC INFORMATION 236 THERAPEUTIC RANGE 241 THERAPEUTIC MONITORING 242 PHARMACODYNAMIC MONITORING 242 DRUG–DRUG INTERACTIONS 244 DRUG–GENE INTERACTIONS 245 MOLECULAR WEIGHTS FOR UNIT CONVERSIONS 247 Ch 12 - CARBAMAZEPINE 250 USUAL DOSAGE RANGE IN THE ABSENCE OF CLEARANCE ALTERING FACTORS 250 GENERAL PHARMACOKINETIC INFORMATION 252 DOSING STRATEGIES 255 THERAPEUTIC RANGE 256 THERAPEUTIC MONITORING 256 PHARMACODYNAMIC MONITORING 257 DRUG–DRUG INTERACTIONS 258 DRUG–DISEASE STATE OR CONDITION INTERACTIONS 259 Ch 13 - DIGOXIN 266 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 266 DOSING STRATEGIES 269 THERAPEUTIC MONITORING 271 PHARMACODYNAMIC MONITORING 272 DRUG–DRUG INTERACTIONS 274 DRUG–DISEASE/CONDITION INTERACTIONS 275 Ch 14 - ETHOSUXIMIDE 278 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 278 GENERAL PHARMACOKINETIC INFORMATION 278 DOSING STRATEGIES 280 THERAPEUTIC RANGE 280 THERAPEUTIC MONITORING 281 PHARMACODYNAMIC MONITORING 281 DRUG–DRUG INTERACTIONS 282 DRUG–DISEASE STATE OR CONDITION INTERACTIONS 282 Ch 15 - UNFRACTIONATED HEPARIN, LOW MOLECULAR WEIGHT HEPARIN, AND FONDAPARINUX 284 UNFRACTIONATED HEPARIN 284 UFH: USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE-ALTERING FACTORS 284 UFH: DOSAGE FORM AVAILABILITY 285 UFH: GENERAL PHARMACOKINETIC INFORMATION 285 DOSING STRATEGIES 287 UFH: THERAPEUTIC RANGE 291 UFH: THERAPEUTIC MONITORING 293 UFH: PHARMACODYNAMIC MONITORING—CONCENTRATION-RELATED EFFICACY 295 UFH: PHARMACODYNAMIC MONITORING—CONCENTRATION-RELATED TOXICITY 295 REVERSING HEPARIN’S EFFECT 296 UFH: DRUG-DRUG INTERACTIONS 297 UFH: DRUG–DISEASE STATE OR CONDITION INTERACTIONS 297 LOW MOLECULAR WEIGHT HEPARINS 297 LMWH: USUAL DOSAGE RANGE IN THE ABSENCE OF CLEARANCE-ALTERING FACTORS 299 LMWH: DOSAGE FORM AVAILABILITY 299 LMWH: GENERAL PHARMACOKINETIC INFORMATION 300 LMWH: DOSING STRATEGIES 300 LMWH: THERAPEUTIC RANGE 301 LMWH: THERAPEUTIC MONITORING 301 LMWH: ASSAY ISSUES 301 LMWH: PHARMACODYNAMIC MONITORING—CONCENTRATION-RELATED EFFICACY 301 LMWH: PHARMACODYNAMIC MONITORING—CONCENTRATION-RELATED TOXICITY 302 LMWH: REVERSING THE EFFECT OF LMWHs 302 LMWH: DRUG–DRUG INTERACTIONS 303 LMWH: DRUG–DISEASE STATE OR CONDITION INTERACTION 303 FONDAPARINUX 304 FONDAPARINUX: DOSAGE RANGE 304 Ch 16 - LIDOCAINE 312 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 312 DOSAGE FORM AVAILABILITY 312 GENERAL PHARMACOKINETIC INFORMATION 314 CLEARANCE 316 HALF-LIFE AND TIME TO STEADY STATE 316 DOSING STRATEGIES 316 THERAPEUTIC RANGE 319 PHARMACODYNAMIC MONITORING: CONCENTRATION RELATED EFFICACY AND TOXICITY 320 DRUG–DRUG INTERACTIONS 320 DRUG–DISEASE STATE OR CONDITION INTERACTIONS 321 Ch 17 - LITHIUM 328 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 328 DOSAGE FORM AVAILABILITY 330 GENERAL PHARMACOKINETIC INFORMATION 330 THERAPEUTIC RANGE 335 THERAPEUTIC MONITORING 335 PHARMACODYNAMIC MONITORING 338 DRUG–DISEASE STATE INTERACTIONS AND SPECIAL POPULATIONS 339 Ch 18 - PHENOBARBITAL 350 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 350 GENERAL PHARMACOKINETIC INFORMATION 351 HALF-LIFE AND TIME TO STEADY STATE 353 THERAPEUTIC RANGE 353 DRUG MONITORING ASSAY CONSIDERATIONS 353 SUGGESTED SAMPLING TIMES AND EFFECT ON THERAPEUTIC RANGE 353 PHARMACODYNAMIC MONITORING—CONCENTRATION RELATED EFFICACY 354 PHARMACODYNAMIC MONITORING—CONCENTRATION RELATED TOXICITY 355 DRUG−DRUG INTERACTIONS 355 DRUG–DISEASE STATE OR CONDITION INTERACTIONS 357 Ch 19 - PHENYTOIN AND FOSPHENYTOIN 360 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 360 DOSAGE FORM AVAILABILITY 361 GENERAL PHARMACOKINETIC INFORMATION 361 THERAPEUTIC RANGE 367 THERAPEUTIC MONITORING 367 PHARMACODYNAMIC MONITORING 368 DRUG–DRUG INTERACTIONS 369 DRUG–DISEASE STATE OR CONDITION INTERACTIONS 370 Ch 20 - THEOPHYLLINE 378 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 378 DOSAGE FORM AVAILABILITY 379 GENERAL PHARMACOKINETIC INFORMATION 379 DOSING STRATEGIES 383 THERAPEUTIC RANGE 384 THERAPEUTIC MONITORING 384 PHARMACODYNAMIC MONITORING 385 DRUG–DRUG INTERACTIONS 387 DRUG–DISEASE STATE OR CONDITION INTERACTIONS 388 Ch 21 - VALPROATE 392 USUAL DOSAGE RANGE IN THE ABSENCE OF CLEARANCE ALTERING FACTORS 392 GENERAL PHARMACOKINETIC INFORMATION 393 DOSING STRATEGIES 396 DOSAGE ADJUSTMENT 396 THERAPEUTIC RANGE 397 EFFECT OF AGE AND PREGNANCY ON THERAPEUTIC RANGE 397 THERAPEUTIC MONITORING 398 PHARMACODYNAMIC MONITORING—CONCENTRATION-RELATED EFFICACY 398 DRUG–DRUG INTERACTIONS 399 DRUG–DISEASE STATE OR CONDITION INTERACTIONS 400 Ch 22 - VANCOMYCIN 404 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 404 DOSAGE FORM AVAILABILITY 405 GENERAL PHARMACOKINETIC INFORMATION 406 DOSING STRATEGIES 408 THERAPEUTIC RANGE 412 THERAPEUTIC DRUG MONITORING 414 PHARMACODYNAMIC MONITORING 414 DRUG–DRUG INTERACTIONS 418 DRUG–DISEASE STATE INTERACTIONS 419 ASSAY ISSUES 422 Ch 23 - WARFARIN 430 USUAL DOSAGE RANGE IN ABSENCE OF CLEARANCE ALTERING FACTORS 431 DOSAGE FORM AVAILABILITY 431 GENERAL PHARMACOKINETIC INFORMATION 432 THERAPEUTIC RANGE 437 THERAPEUTIC MONITORING 438 PHARMACODYNAMIC MONITORING 439 DRUG–DRUG INTERACTIONS 441 DRUG–DISEASE STATE OR CONDITION INTERACTIONS 442 App A - THERAPEUTIC RANGES OF DRUGS IN TRADITIONAL AND SI UNITS 452 App B - NONDRUG REFERENCE RANGES FOR COMMON LABORATORY TESTS INTRADITIONAL AND SI UNITS 454 INDEX 456