Cost-effectiveness of therapeutic drug monitoring: a systemic review. Since these systems are real-time in nature, specification of temporal constraints is a key issue. The site is secure. The use of TDM requires a combined approach encompassing pharmaceutical, pharmacokinetic, and pharmacodynamic techniques and analyses. CiteSeerX - Document Details (Isaac Councill, Lee Giles, Pradeep Teregowda): Embedded systems are application specific digital systems that are usually designed using a microprocessor along with a set of programmable hardware and software components. Packaging and transporting specimens to the laboratory - inpatients and outpatients. Transdermal absorption can be enhanced by placing the drug in an oil and rubbing it on the skin. Wherever possible, the assay performance should be evaluated using an external quality assurance program that provides a rapid turn-around time for results and comprehensive feedback on the assay performance, and that has a large number of subscribers. Of note, intermuscular injection of a drug does not guarantee bioavailability because blood perfusion of the muscular site may be low. Oxalate is both endogenous and dietary. It is a quick route to deliver drugs to blood circulation and the patient should achieve the targeted blood concentration for appropriate therapy. When initiating drug therapy, the physician may find it useful to measure the plasma drug concentration and tailor the dosage to the individual. Measuring the plasma drug concentration may guide clinicians to stop treatment under two known circumstances. Kearns GL, Moss MM, Clayton BD, Hewett DD. Medical Devices . Therefore, those patients who are the most strongly motivated to minimize their kidney stone risk long-term and are likely to continue treatment long term will receive the most benefit from this testing. Pharmacogenetics describes how genetics can impact drug metabolism and the clinical effect of the drug. Performance characteristics of four immunoassays for antiepileptic drugs on the IMMULITE 2000 automated analyzer. Sym D, Smith C, Meenan G, Lehrer M. Fluorescence polarization immunoassay: can it result in an overestimation of vancomycin in patients not suffering from renal failure? Even for drugs that fulfill these criteria, some controversy exists about the usefulness of monitoring their plasma concentrations [20]. Commonly used specimens for wildlife disease investigations include intact carcasses, tissues from carcasses, euthanized or moribund animals, parasites, ingested food, feces . Roughly a third of calcium stone formers will have elevated urine oxalate. The purpose of drug metabolism is to convert drugs into more hydrophilic metabolites to enhance elimination from the body. Wu SL, Li W, Wells A, dasgupta A. Digoxin-like and digitoxin-like immunoreactive substances in elderly people: impact on therapeutic drug monitoring of digoxin and digitoxin concentrations. Therapeutic drug monitoring can be used to evaluate the clinical presentation of the patient and to monitor decontamination efforts for patients with toxicity. The advantage of chromatographic methods such as liquid chromatographytandem mass chromatography is the ability to simultaneously analyze multiple drugs in a single assay and methods typically provide higher specificity for identification of the drug. Enteric hyperoxaluria can be a significant risk factor for patients with inflammatory bowel disease, cystic fibrosis, pancreatic insufficiency, or previous bariatric bowel surgery. Evaluating the quality of medical care. Correspondence to Ju-Seop Kang, MD. The interpretation of urine chemistry requires reference ranges. mobilize glycogen from the live. If the dosage regimen must be altered for any reason at a later stage of treatment, for example, in patients with renal failure, measuring plasma concentrations again may be helpful. An appropriate pharmacokinetic evaluation requires the acquisition of properly timed blood specimens [41]. Interpretation is complex and often subjective due to this variability. This dictum applies particularly to lithium in preventing manic-depressive attacks, to phenytoin in preventing fits after neurosurgery or trauma, and to cyclosporine in preventing transplant rejection. Decreased urine volume is a major risk factor for stone disease as concentrated urine raises the supersaturation of all stone-forming salts. In large chemical pathology laboratories staffed by highly skilled scientists and equipped with state-of-the art automated analyzers, many clinicians assume that the results will be accurate. Notably, the important overlap between "toxic" and "nontoxic" plasma concentration values limits use of the method in the diagnosis of digitalis toxicity (Fig. Clinical pharmacists and pharmacologists use pharmacokinetic principles to assess these interpretations. Bioavailability is the percentage of a drug from the original drug product that enters the circulation in an unchanged - non-metabolized - form. Aronson and Hardman [20] determined that a dosage selection based on plasma drug concentration assessment led to a decrease of digitalis toxicity to below 4%. Before the patients specimen is collected, it is important to determine the appropriate timing of specimen collection and the appropriate specimen type. Peak plasma concentrations are helpful in evaluating the dose of antibiotics used to treat severe, life-threatening infections. Accessibility To summarize, TDM results are impacted by factors that affect pharmacokinetics and pharmacodynamics, such as age and gender, nutrition, pharmacogenetics, body weight, pregnancy, disease, drug-drug and food-drug interactions. Used to monitor drug therapy, blood glucose levels, and other laboratory tests. Serum samples, usually calcium, potassium, uric acid, and phosphorus, are sometimes also included in the study. Supersaturation ratios for various stone types can then be calculated. Therefore, measuring the plasma concentration of a drug allows the doctor to track the dosage to the individual patient and to obtain the maximum therapeutic effect with minimal risk of toxicity. Results are combined with detailed medical and dietary history, serum chemistry, and stone composition to guide prophylactic stone-reducing treatment. First, it is vital to obtain the blood sample for measuring the drug concentration at the correct time after dosing. Drugs can be absorbed into the blood stream by several routes of administration. Once the analysis is complete, a detailed report of the results is provided to the ordering clinician. Collecting a sample for a full 24 hours can be difficult for some patients and is certainlyinconvenient. The laboratory must ensure that the assay used is as reliable and specific as possible and that appropriate quality control is undertaken. Question: Bacteremia. Levy G. Pharmacologic target-mediated drug disposition. Indications for requesting plasma drug concentrations. Patient demographic characteristics are critically important so that the contributions of age, disease state, ethnicity, and other variables to inter-individual variation in pharmacokinetics and pharmacodynamics can be considered. For example, when giving a thiazide diuretic to a patient taking lithium, measuring the plasma lithium concentrations is helpful to avoid toxicity. Glazko AJ. Extending Donabedian's analysis to TDM, with of structural components include the TDM testing equipment and facilities, qualifications of the clinical and laboratory staff, the presence of a TDM service, monitoring supervision, and administrative organization. what specimen requires chilling during transfer to the lab. , The Journal of Applied Laboratory Medicine, HLA Testing for Solid Organ Transplantation, Laboratory Testing for Transgender Individuals, Maple Syrup Urine Disease and Other Disorders of Branched Chain Amino Acid Catabolism, Procalcitonin Testing and Antibiotic Stewardship, Setting Analytical Quality Goals with Biological Variation Data, Tyrosinemias Biochemistry and Clinical Laboratory Investigation, Clinical Chemistry Guide to Scientific Writing, Commission on Accreditation in Clinical Chemistry, Discuss the rationale for therapeutic drug monitoring, which I will refer to as (TDM), Describe how drug therapy is impacted by pharmacokinetics, pharmacodynamics and pharmacogenetics, I will List various classes of drugs that require TDM, And Discuss analytical methods available for TDM. Low urine magnesium is typically dietaryin origin. Antiepileptic drug monitoring at the epilepsy clinic: a prospective evaluation. In: Rowald M, Sheiner LB, Steiner JL, editors. and transmitted securely. Outcomes assessment of therapeutic drug monitoring. Bootman JL, Wertheimer AI, Zaske D, Rowland C. Individualizing gentamicin dosage regimens in burn patients with gram-negative septicemia: a cost-benefit analysis. Mississippi mud no more: cost-effectiveness of pharmacokinetic dosage adjustment of vancomycin to prevent nephrotoxicity. Blood or plasma concentrations change throughout a dosage interval, and the time of the blood sample draw relative to the time of dose administration must be known to enable sensible interpretation. AACC uses cookies to ensure the best website experience. In such instances the metabolite should also be measured because it is contributing to the effect of the drug on the patient. Accurate collections can detect treatable abnormalities predisposing to nephrolithiasis, glomerulonephritis or the nephrotic syndrome and help monitor treatment progress. The fact that patients typically feel no better on treatment makes it far more challenging to keep patients on therapy long term. Birkett DJ. Pioneers of drug monitoring in the 1970s focused on adverse drug reactions and demonstrated clearly that by constructing therapeutic ranges, the incidence of toxicity to drugs such as digoxin [8], phenytoin, lithium, and theophylline [9] could be reduced [10]. Immunoassay methods are less labor intensive and have faster turnaround time to result than chromatographic methods for measuring a single analyte. The recommended drug classes for therapeutic drug monitoring include: Antiarrhythmics, Antibiotics, Anti-cancer drugs, Antidepressants, Antiepileptics Antipsychotics, Bronchodilators, Cardiac drugs, HIV drugs, Immunosuppressant drugs and Lithium Pharmacoeconomics and therapeutic drug monitoring. Information about plasma concentration is helpful for a number of drugs in clinical practice. The average daily excretion of creatinine for males is 18 to 24 mg/kg and 15 to 20 mg/kg for females. It is important to note that TDM services should be based on the needs of clinicians and clinical studies from the literature. Proper collection and transport of specimens is critical to the quality of results produced by the laboratory. Therapeutic drug monitoring (TDM) is the clinical practice of measuring specific drugs at designated intervals to maintain a constant concentration in a patient's bloodstream, thereby optimizing individual dosage regimens. If the potential for a drug interaction is suspected, then measurement of the plasma concentration may guide subsequent changes in dosage. A chemical composition analysis of any stone material is very helpful if available. Medical Dictionary for the Health Professions and Nursing Farlex 2012 To track these responses, we present seven primary insect sampling methodsmalaise trapping, light trapping, pan trapping, pitfall trappings, beating sheets, acoustic monitoring, and active visual surveysand recommend standards while highlighting examples of model programs. Drug can also be distributed to different reservoirs in the body. Over the last 30 years, in response to the lessons learned from using TDM and growing concerns among clinicians and the public about rising health care costs, the principles of pharmacoeconomics are now being applied to various fields, including TDM [43]. Continuing without changing cookie settings assumes you consent to our use of cookies on this device. For TDM to be effective, the drug concentration must be accurate and precise. Drugs administered intravenously will bypass first-pass metabolism in the liver and have 100% bioavailability in systemic circulation. Destache CJ, Meyer SK, Bittner MJ, Hermann KG. Lower sodium diets typically allow for up to 1500 mg of dietary sodium per day. A pharmcoeconomic analysis of the impact of TDM in adult patients with generalized tonic-clonic epilepsy showed that patients undergoing TDM had much more effective seizure control, fewer adverse events, better earning capacity, lower costs to the patient, savings from lower hospitalizations per seizure, and greater chances of remission [48]. Molecular Based Tests Used in Diagnostic Laboratories 33 Depending on the nucleic basis of the test, RNA versus DNA, this will also impact on the time between specimen collection and sample storage. Absolute time was likewise abolished after Einstein re-analysed what it means when we say two events happen at the same time, and then went on to derive special relativity. Any . Shaw LM, Kaplan B, Brayman KL. Some clinically important aspects of serum protein binding of drugs that should be noted: As the free drug concentration decreases, the pharmacologic activity decreases and the drug clearance decreases. Human Genome Project and pharmacogenomics: implication for pharmacy. 2) [20]. The Human Genome Project. As a library, NLM provides access to scientific literature. Aronson JK, Hardman M. ABC of monitoring drug therapy: measuring plasma drug concentrations. The stability of drugs after collection also may vary, and can be impacted by collection tube preservatives, temperature, light, freeze thaw cycles, and interferences, such as lipids, bilirubin and hemoglobin. Low urinary citrate levels in the setting of thiazide therapy may correlate with hypokalemia. For example, it is relatively easy to recognize acute phenytoin toxicity, and measuring the plasma concentration may not be necessary for diagnosis, although it may be helpful in adjusting the dosage subsequently. Twenty-four-hour urine testing is not curative, but it does direct effective prophylactic treatment for those who are willing to follow therapeutic guidelines on a long-term basis. Impact of goal-oriented and model-based clinical pharmacokinetic dosing of aminoglycosides on clinical outcome: a cost-effectiveness analysis. Therapeutic drug monitoring beyond 2000. BC collection involves. Nonpolar drugs are lipid soluble. Another term in pharmacokinetics is volume of distribution (Vd), which relates to the amount of drug in the body to the concentration of drug in the blood. Thus, measuring aminoglycoside plasma concentrations may help to distinguish between toxicity and infection. 2018 Nov 26 [PubMed PMID: 30473581], Rsimont G,Gadisseur R,Lutteri L,Krzesinski JM,Cavalier E,Delanaye P, [How I explore a proteinuria]. Thus, the role of many drug assay laboratories is to measure the concentration of a therapeutic drug in a blood sample and relate this number to a therapeutic range published in the literature. Reduction of digoxin toxicity associated with measurement of serum levels: a report from the Boston Collaborative Drug Surveillance program. Clinical laboratory regulations require temperature monitoring of facilities, reagent and specimen storage, as well as temperature-dependent equipment. The assay results should be available quickly, preferably within 24 h of receiving the sample, as the most important uses of the measurements are during dosage adjustments and in diagnosing toxicity, when rapid decisions must be made. 900 Seventh Street, NW Suite 400 That is where timespec is defined in my . Tel: 82-2-2220-0652, Fax: 82-2-2292-6686, This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, Drug monitoring, therapeutic; Pharmacokinetics. Spector R, Park GD, Johnson GF, Vesell ES. Potassium citrate supplements should result in marked increases in urinary potassium secretion. Neonatal pharmacodynamics-basic principles: II. The role of TDM is important for drugs with variability in the rate of metabolism in different patients of the general population that may have a single nucleotide mutation in the gene for the drug metabolism enzymes. Drug monitoring is employed to ensure that the patients drug concentrations are within the therapeutic range. After 5 half-lives, over 95% of a drug will have accumulated, and for practical purposes, steady state has been achieved. The Journal of urology. DeVore KJ, Hobbs RA. This route can also be used to administer drugs to children and elderly patients. sharing sensitive information, make sure youre on a federal For many drugs, there are severe toxicities that occur at sub-lethal doses in humans, and these toxicities often limit the maximum dose of a drug. Analytical goals in therapeutic drug monitoring. Most such assay interferences are the result of cross-reactivity with the drug's metabolites, but in some cases, endogenous compounds or drugs with similar structures can cross-react, resulting in either a falsely elevated or decreased assayed drug concentration reading [35-39]. Dipiro JT, Spruill WJ, Blouin RA, et al. https://creativecommons.org/licenses/by-nc/4.0, http://www.medscape.com/medscape/CNO/2000/APHA/APHA-04.htm. However, drugs with long half-lives should be monitored before steady state is achieved to ensure that individuals with impaired metabolism or renal excretion are not at risk of developing toxicity at the initial dosage regimen prescribed, as can occur with amiodarone and perhexiline. Reviews in urology. The therapeutic index is used as a measure of the relative safety of the drug for a particular treatment. Over the last two decades a growing number of neuroscience labs are conducting behavioral assays in rodents. 1) [16,17]. However, this argument merely emphasizes the need for proper interpretation of plasma drug concentrations under such conditions [19]. The most commonly used procedures are fluorescence polarization immunoassay (FPIA), enzyme immunoassay (EMIT), and enzyme-linked immunosorbant assay (ELISA) [31,32]. The use of low ISI thromboplastin serves to improve the precision of therapeutic monitoring by enhancing sensitivity of the prothrombin assay. Therapeutic drug measuring is only one part of TDM that provides expert clinical interpretation of drug concentration as well as evaluation based on pharmacokinetic principles. If the drug has been administered by bolus injection, samples should be taken at least 1 h post-dosage to avoid overlapping the distribution phase. Frank EL, Schwarz EL, Juenke J, et al. Gross AS. Ohning BL. Urine calcium concentration is dependent on dietary calcium, sodium intake, and protein intake. You will then receive an email that helps you regain access. Burton ME, Shaw LM, Schentag JJ, Evans WE. This is not true for other drugs, particularly phenytoin. Cristodorescu R, Deutsch G, Dragan S. Clinical utility of plasma digoxin measurements. Reynolds DJ, Aronson JK. 2018 Oct [PubMed PMID: 30335258], Mohammadi Sichani M,Jafarpisheh A,Ghoreifi A, Evaluation and Comparison of Metabolic Disorders between Patients with Unilateral and Bilateral Staghorn Renal Stones. For a limited number of drugs for which there is a better relationship between plasma or blood concentration-response than dose-response, the measurement of plasma or blood concentrations has become a valuable surrogate index of drug exposure in the body [16]. The indications for drug monitoring have widened to include efficacy, compliance, drug-drug interactions, toxicity avoidance, and therapy cessation monitoring [18, 19] (Table 1). Specialized testing is also available for pediatric patients and patients with cystinuria. Over 90% of kidney stone patients tested will demonstrate at least one chemical disorder that is sub-optimal. // Borowitz SM. Drugs can also alter how the body absorbs, metabolizes or excretes another drug. Note that this use of the plasma concentration measurement depends on the concept that there is a lower end to the therapeutic range. Criteria that a drug should satisfy for plasma concentration measurements to be useful. You may need testing when you first start taking a medicine. Vozeh S. Cost-effectiveness of therapeutic drug monitoring. Review Article Laboratory testing and services have an important role in the provision of health care and in utilization and reimbursement. Withdrawal of lithium and the use of a different treatment would be justified. Urine chemistry is a continuous variable making the strict cut-off points and abnormal values somewhat arbitrary. Ensom MH, Davis GA, Cropp CD, Ensom RJ. In patients with a history of cystine stones or a positive cystine cyanide test, 24-hour cystine levels can also be measured.[5][6]. Urine pH is a critical data point as changes in urine pH can drive the crystallization of certain salts. Pharmacokinetics made easy: therapeutic drug monitoring. For this reason, vitamin C supplements should be limited to 1000 mg or less daily. In: Dipiro JT, editor. As urinary constituents reach outside of normal or optimal ranges, the lithogenic risk increases.[7]. 2Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea. Therapeutic drug monitoring reduces toxic drug reactions: a meta-analysis. The clinician presenting a drug assay request must communicate these details effectively to the members of the TDM team. You can change these settings at any time, but that may impair functionality on our websites. Once the decision to monitor the concentration of a therapeutic drug has been made, it is important that a biological sample is collected to provide a clinically meaningful measurement. If the sample required is plasma to be used in an RNA based assay, whole blood should be spun down and plasma removed for On the other hand, digoxin toxicity may mimic certain symptoms of heart disease, and measuring the plasma concentration in cases in which toxicity is suspected may be helpful in confirming the diagnosis. There is no justification for routine measurements of plasma drug concentrations without a definite purpose. warm the sample tube for 30 min before collection. The drug molecule can be metabolized by phase I reactions, which alter chemical structure by oxidation, reduction, or hydrolysis. Although serum is the preferred sample for monitoring of many drugs, there are different collection tubes are available that include plastic tubes without additives as well as specialized serum separator tubes that contain a gel to separate serum from the cellular components after centrifugation. The science of TDM introduced a new aspect of clinical practice in the 1960s with the publication of initial pharmacokinetic studies linking mathematical theories to patient outcomes [3]. Shenfield GM. Neonatal pharmacodynamics-basic principles: I. drug delivery. Volume of distribution is a theoretical volume in the body to contain the total amount of drug administered at the same concentration in serum or plasma. Several criteria must be satisfied for the plasma concentration of a drug to be useful. National Library of Medicine Over the first decade, many consensus documents have been published that address the need for and methodology of immunosuppressive drug monitoring, with the most recent publication including important guidelines and recommendations for cyclosporine, silorimus, and tacrolimus adminiatration [56]. This information can be used to identify the most appropriate dosage regimen to achieve the optimal response with minimal toxicity [57,58]. On the other hand, if it is difficult to measure the therapeutic effects of a drug, then measuring the plasma concentration helps to tailor the dose within the appropriate therapeutic range. If a patient is administered a drug repeatedly, the drug and its metabolites will accumulate in the body. The liver may extensively metabolize a drug before it reaches the systemic circulation, leading to low oral bioavailability, which is called the first-pass effect. Collins FS. The https:// ensures that you are connecting to the Assessing the quality of laboratory services using quality indicators or performance measures requires a systematic, transparent, and consistent approach to collecting and analyzing data. The appropriate use of TDM requires more than a simple measurement of patient blood drug concentration and a comparison to a target range. There are four steps involved in obtaining a good quality specimen for testing: (1) preparation of the patient, (2) collection of the specimen, (3) processing the specimen, and (4) storing and/or transporting the specimen.
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