9.22 Therapeutic Drug Monitoring

Immunoassays are important for therapeutic drug monitoring during long-term drug therapy, to balance the drug concentration in the body to achieve efficacy while avoiding toxic side-effects.

Abstract

This chapter provides a review of the use of immunoassay in therapeutic drug monitoring. The immunoassay technology commonly used in this field is described: radioimmunoassay [not used much now], enzyme-multiplied immunoassay technique, cloned enzyme donor immunoassay, enzyme-linked immunosorbent assay, homogeneous fluorescence enhancement and quenching assays, fluorescence polarization and microparticle enzyme immunoassay. Measurement of free drug concentration is reviewed and there is a section on practical aspects and assay interferences. The drugs are then reviewed in individual sections with these subsections: clinical applications, mode of administration, pharmacological effects, pharmacokinetics, therapeutic range, potentially toxic concentration, side effects and type of sample. The drugs described are: acecainide (n-acetylprocainamide), digoxin, digitoxin, procainamide, quinidine, theophylline, amikacin, gentamicin, tobramycin, vancomycin, carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin (diphenylhydantoin), primidone, topiramate, valproic acid, zonisamide, ciclosporin (cyclosporin), methotrexate, mycophenolic acid, sirolimus, tacrolimus, acetaminophen (paracetamol), and the tricyclic antidepressants amitriptyline, imipramine and desipramine.

Contributors

Professor Philip A Routledge is currently Professor of Clinical Pharmacology and Head of the Department of Pharmacology, Therapeutics and Toxicology in Cardiff University School of Medicine. He graduated MB BS (1972) and MD (1978) from the University of Newcastle upon Tyne, England. Since 1981, he has been an honorary consultant general physician, clinical pharmacologist and clinical toxicologist at University Hospital Llandough, in Cardiff, Wales. His research interests are in the safe, effective and cost-effective use of medicines. He has published widely on the use of free and total concentrations of drugs in monitoring treatment. He is Chairman of the All Wales Medicines Strategy Committee and of the UK Herbal Medicines Advisory Committee. He is also presently President of the British Pharmacological Society. In 2008, He was appointed Officer of the Order of the British Empire (OBE) for Services to medicine.

With over 30 years experience in the fields of analytical toxicology and medical informatics, Dr. Alun Hutchings has worked for the NHS and NPIS during his career, and has been Consultant Analytical Toxicologist and Head of the Cardiff Toxicology Laboratories since 2001. He holds a PhD in pharmacology, and is a Chartered Scientist (CSci) and a Fellow of the Institute of Biomedical Sciences (FIBMS).  Having a particular interest in the analysis of designer drugs and legal highs, Dr Hutchings recently co-founded the WEDINOS group (Welsh Emergency Departments Investigation of Novel Substances).

Keywords

Therapeutic drug, therapeutic drug monitoring, absorption, distribution, excretion, metabolism, therapeutic ratio, therapeutic range, toxicity, side effect, radioimmunoassay, enzyme-multiplied immunoassay technique, cloned enzyme donor immunoassay, enzyme-linked immunosorbent assay, fluoroimmunoassay, fluorescence enhancement, quenching, fluorescence polarization, homogeneous immunoassay, microparticle enzyme immunoassay, free drug, interference, cross-reactivity, pharmacokinetics, antiarrhythmic agent, acecainide, n-acetylprocainamide, digoxin, digitoxin, procainamide, quinidine, theophylline, antibiotics, amikacin, gentamicin, tobramycin, vancomycin, anticonvulsant, carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, diphenylhydantoin, primidone, topiramate, valproic acid, zonisamide, ciclosporin, cyclosporin, methotrexate, mycophenolic acid, sirolimus, tacrolimus, acetaminophen, paracetamol, tricyclic antidepressant, amitriptyline, imipramine, desipramine.

Recent Review

Saitman, A., Park, H-D., & Fitzgerald, R.L. False-positive interferences of common urine drug screen immunoassays: a review. J. Anal. Toxicol. Doi: 10.1093/jat/bku075.