Optimization and Validation of a Chromatographic Method for the Quantification of Isoniazid in Urine of Tuberculosis Patients According to the European Medicines Agency Guideline

Isoniazid is a drug that is widely used against tuberculosis. However, it shows high interpatient variability in metabolism kinetics and clinical effect, which complicates the prescription of the medication and jeopardizes the success of the therapy. Therefore, in a specific patient, the pharmacokinetics of the drug must be elucidated to decide the proper dosage and intake frequency to make the drug suitable for therapeutic drug monitoring. This can be performed by the quantification of the drug in urine as this process is non-invasive and allows the effects of long-time exposure to be inferred. The paper describes the development of a micellar liquid chromatographic method to quantify isoniazid in urine samples. Extraction steps were avoided, making the procedure easy to handle and reducing the waste of toxic organic solvents. Isoniazid was eluted in less than 5 min without interference from other compounds of the urine using a mobile phase containing 0.15 SDS–12.5% 1-propanol (v/v)–Na2HPO4 0.01 M buffered at pH 7, running at 1 mL/min under isocratic mode through a C18 column with the detection wavelength at 265 nm. The method was validated by following the requirements of the Guidelines on Bioanalytical Method Validation issued by the European Medicines Agency (EMA) in terms of selectivity, calibration curve (r2 = 0.9998 in the calibration range (0.03–10.0 μg/mL), limit of detection and quantification (10 and 30 ng/mL respectively), precision (<16.0%), accuracy (−0.9 to +8.5%), carry-over, matrix effect, and robustness. The developed method was applied to quantify isoniazid in urine samples of patients of an Indian hospital with good results. The method was found to be useful for routine analysis to check the amount of isoniazid in these patients and could be used in its therapeutic monitoring.

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Probability Assessment Approach to Therapeutic Drug Monitoring: Tobramycin

DICP ◽

10.1177/106002808902300311 ◽

1989 ◽

Vol 23 (3) ◽

pp. 240-244 ◽

Cited By ~ 1

Author(s):

Richard L. Slaughter

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Cost Benefit ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Probability Assessment ◽

Serum Concentrations ◽

Specific Patient ◽

Assessment Approach ◽

Toxic Concentrations

Pharmacokinetic monitoring is an important therapeutic goal of aminoglycoside therapy. The overall goal of this study was to identify specific patient groups that would derive the maximum benefit from therapeutic drug monitoring services. These groups are patient populations with high probabilities of achieving toxic or subtherapeutic concentrations. Out of a total population of 86 stable, noncritically ill patients, 27 toxic concentrations (trough >2.0 μg/mL) occurred in 15 patients. In comparison to patients (n = 46) with therapeutic concentrations (trough < 2.0 μg/mL, peak >4.0 μg/mL), these patients were older (64 ± 11 vs. 54 ± 18years; p < 0.02) and had a higher percentage of females (66.7 vs. 37 percent; p < 0.05). Those patients with subtherapeutic concentrations (43 concentrations in 25 patients) had higher estimated creatinine clearance values than those with therapeutic concentrations (94 ± 45 vs. 74 ± 27 mL/min; p < 0.005). Probability assessment analysis of the data showed a sevenfold increase in toxic concentrations in patients above 50 years. Females over age 50 had 2.3 times the risk of developing toxic concentrations as males over age 50. In contrast, the development of low concentrations was not predicted by age or sex. Underdosage by ≥30 percent was a reasonable predictor (75 percent) of low peak concentrations. Furthermore, toxic concentrations did not occur in patients who were underdosed, justifying dosage increases prior to obtaining serum concentrations in these patients. The group with the highest probability of attaining therapeutic concentrations was males receiving therapeutic doses who were under age 50 (85.5 percent). Therefore, routine measurement of serum concentrations in this group would have limited cost-benefit potential. It is concluded that a probability assessment approach can be used to facilitate the therapeutic monitoring of tobramycin.

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Therapeutic Monitoring of Anticonvulsant Drugs: Gas-Chromatographic Simultaneous Determination of Primidone, Phenylethylmalonamide, Carbamazepine, and Diphenylhydantoin

Clinical Chemistry ◽

10.1093/clinchem/21.11.1658 ◽

1975 ◽

Vol 21 (11) ◽

pp. 1658-1662 ◽

Cited By ~ 11

Author(s):

Charles J Least ◽

George F Johnson ◽

Harvey M Solomon

Keyword(s):

Simultaneous Determination ◽

Standard Method ◽

Chromatographic Method ◽

Limit Of Detection ◽

Internal Standard ◽

Normal Serum ◽

Therapeutic Monitoring ◽

The Mean ◽

Gas Chromatographic Method

Abstract We describe a sensitive and precise gas-chromatographic method in which benzylmalonate methylester monoamide is used as the internal standard for the simultaneous determination of primidone, phenylethylmalonamide, carbamazepine, and diphenylhydantoin. The trimethylsilyl derivatives of the anticonvulsants are well separated from each other and from normal serum constituents. The lower limit of detection for each drug is 0.5 mg/liter when 1 ml of serum is analyzed. Withinrun precision (CV), established by analysis of 10 replicates, was as follows: primidone (5.4 mg/liter), 2.6%; phenylethylmalonamide (5.5 mg/liter), 1.6%; diphenylhydantoin (6.6 mg/liter), 3.8%; and carbamazepine (10.4 mg/liter), 3.2%. Fifty specimens were analyzed for primidone and 35 for diphenylhydantoin by a standard gas-chromatographic method involving on-column methylation and by the procedure we have developed. The mean value observed for primidone with the on-column alkylation procedure was 9.3 mg/liter and with our procedure was 9.6 mg/liter. When values for our assay were regressed against values for the standard method, the slope of the least-squares line was 0.936, the intercept was 1.00 mg/liter, and r was 0.939. The mean values observed for diphenylhydantoin by on-column methylation and with our procedure were both 12.6 mg/liter. When values for our assay were regressed against the standard method, the slope of the leastsquares line was 0.944, the intercept was 0.3 mg/liter, and r was 0.988

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Point of Care Method for the Determination of Dabigatran in Urine Samples From Patients On Treatment.

Blood ◽

10.1182/blood.v120.21.2270.2270 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2270-2270 ◽

Cited By ~ 1

Author(s):

Job Harenberg ◽

Sandra Kraemer ◽

Shanshan Du ◽

Christina Giese ◽

Roland Kraemer

Keyword(s):

Limit Of Detection ◽

Point Of Care ◽

Patent Application ◽

Plasma Concentrations ◽

Urine Samples ◽

Plasma Samples ◽

Specific Patient ◽

Cutoff Value ◽

Healthy Persons

Abstract Abstract 2270 Dabigatran is effective and safe for prevention of thromboembolism in several indications at daily fixed doses not requiring laboratory dose adjustment. However, it may be necessary to determine its activity/concentration in specific patient populations by specific assays from plasma samples. A point of care (POC) method may offer advantages by providing immediate results to facilitate medical decisions for acute therapeutic interventions. Plasma and urine samples were taken from patients on treatment with 110mg or 150mg dabigatran bid (n=110) and healthy persons (n=144) after having given written informed consent. Dabigatran was purified from commercially available Pradaxa® and its purity was characterized by analytical methods and S2238 thrombin specific chromogenic substrate assay and Hemoclot assay containing dabigatran standards. The S2238 assay was also used for the determination of dabigatran in plasma samples of patients and healthy persons using one purified dabigatran as standard. The lower limit of detection was 0.06μg/ml plasma. In urine dabigatran was determined by a POC method incubating the lyophilized reagents on mini-strips followed by incubation with patient‘s urine (international patent application No PCT/EP2012/002540). The development of colour of urine samples was determined 10 min after incubation with reagents quantitatively by optical density (OD) measurement and qualitatively as judged by eye according negative and positive colour (three independent readings by SD, SK, CG, and photographic documentation). To determine the positive and negative predictive value (PPV and NPV) of plasma samples, a cutoff value of <0.06μg/ml dabigatran was defined. The PPV and NPV of POC method was determined for urine samples of the control and treatment group according positive and negative development of colour as judged by eye reading. Control persons (n=144) displayed plasma concentrations of 0.04+0.03 μg/ml (mean, standard deviation) of whom 128 had values below the cutoff value <0.06 μg/ml. Sixteen patients had values above this cutoff. Accordingly, the NPV for correct negative results in controls was 88.9%. In patients on therapy the concentration of dabigatran was 0.12+0.08 μg/ml (n=107). 102/107 patients had plasma concentrations of dabigatran above the cutoff value of 0.06 μg/ml and 5 patients below the cutoff-value. This results in a PPV of 95.4%. Using the POC method for dabigatran in urine all of 144 control persons had negative values with OD measurement (0.803+0.116 OD units) and eye measurement. The NPV for control persons was 100%. During therapy with dabigatran, all 110 patients had positive colour development as judged by eye corresponding to an OD of 0.219+0.161. Accordingly, the PPV was 100% for patients on treatment with dabigatran. Limitations of the POC methods are the lack of information about the compliance of the patient and severe renal impairment. The validation of the POC assay by patients is ongoing. The POC method of patients on treatment with dabigatran improves the NPV and PPV from about 90% with plasma samples to 100% using urine samples, respectively. The method is non-invasive, rapid, and specific, can be repeatedly performed and may be used by medical personal and patients. The development of colour is different from the POC method for rivaroxaban. Disclosures: No relevant conflicts of interest to declare.

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Simultaneous Measurement of Tricarboxylic Acid Cycle Intermediates in Different Biological Matrices Using Liquid Chromatography–Tandem Mass Spectrometry; Quantitation and Comparison of TCA Cycle Intermediates in Human Serum, Plasma, Kasumi-1 Cell and Murine Liver Tissue

Metabolites ◽

10.3390/metabo10030103 ◽

2020 ◽

Vol 10 (3) ◽

pp. 103 ◽

Cited By ~ 2

Author(s):

Ramji Rathod ◽

Bharat Gajera ◽

Kenneth Nazir ◽

Janne Wallenius ◽

Vidya Velagapudi

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Limit Of Detection ◽

Tricarboxylic Acid Cycle ◽

Tca Cycle ◽

Tricarboxylic Acid ◽

European Medicines Agency ◽

Bioanalytical Method Validation ◽

Aconitic Acid ◽

Tca Cycle Intermediates

The tricarboxylic acid (TCA) cycle is a central part of carbon and energy metabolism, also connecting to glycolysis, amino acid, and lipid metabolism. The quantitation of the TCA cycle intermediate within one method is lucrative due to the interest in central carbon metabolism profiling in cells and tissues. In addition, TCA cycle intermediates in serum have been discovered to correspond as biomarkers to various underlying pathological conditions. In this work, an Liquid Chromatography-Mass Spectrometry/Mass Spectrometry-based quantification method is developed and validated, which takes advantage of fast, specific, sensitive, and cost-efficient precipitation extraction. Chromatographic separation is achieved while using Atlantis dC18 2.1 mm × 100 mm, particle size 3-μm of Waters column with a gradient elution mobile phase while using formic acid in water (0.1% v/v) and acetonitrile. Linearity was clearly seen over a calibration range of: 6.25 to 6400 ng/mL (r2 > 0.980) for malic acid; 11.72 to 12,000 ng/mL (r2 > 0.980) for cis-aconitic acid and L-aspartic acid; 29.30 to 30,000 ng/mL (r2 > 0.980) for isocitric acid, l-serine, and l-glutamic acid; 122.07 to 125,000 ng/mL (r2 > 0.980) for citric acid, glycine, oxo-glutaric acid, l-alanine, and l-glutamine; 527.34 to 540,000 ng/mL (r2 > 0.980) for l-lactic acid; 976.56 to 1,000,000 ng/mL (r2 > 0.980) for d-glucose; 23.44 to 24,000 ng/mL (r2 > 0.980) for fumaric acid and succinic acid; and, 244.14 to 250,000 ng/mL (r2 > 0.980) for pyruvic acid. Validation was carried out, as per European Medicines Agency (EMA) “guidelines on bioanalytical method validation”, for linearity, precision, accuracy, limit of detection (LOD), limit of quantification (LLOQ), recovery, matrix effect, and stability. The recoveries from serum and tissue were 79–119% and 77–223%, respectively. Using this method, we measured TCA intermediates in serum, plasma (NIST 1950 SRM), and in mouse liver samples. The concentration found in NIST SRM 1950 (n = 6) of glycine (246.4 µmol/L), l-alanine (302.4 µmol/L), and serine (92.9 µmol/L).

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182. Missed Opportunities to Discontinue Unnecessary Vancomycin During Pharmacist Therapeutic Monitoring

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.226 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S98-S98

Author(s):

Corey J Medler ◽

Mary Whitney ◽

Juan Galvan-Cruz ◽

Ron Kendall ◽

Rachel Kenney ◽

...

Keyword(s):

Length Of Stay ◽

Adverse Drug Events ◽

Academic Medical Center ◽

Total Duration ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Therapeutic Monitoring ◽

Resistant Bacteria ◽

Therapeutic Drug ◽

Missed Opportunities

Abstract Background Unnecessary and prolonged IV vancomycin exposure increases risk of adverse drug events, notably nephrotoxicity, which may result in prolonged hospital length of stay. The purpose of this study is to identify areas of improvement in antimicrobial stewardship for vancomycin appropriateness by clinical pharmacists at the time of therapeutic drug monitoring (TDM). Methods Retrospective, observational cohort study at an academic medical center and a community hospital. Inclusion: patient over 18 years, received at least three days of IV vancomycin where the clinical pharmacy TDM service assessed for appropriate continuation for hospital admission between June 19, 2019 and June 30, 2019. Exclusion: vancomycin prophylaxis or administered by routes other than IV. Primary outcome was to determine the frequency and clinical components of inappropriate vancomycin continuation at the time of TDM. Inappropriate vancomycin continuation was defined as cultures positive for methicillin-susceptible Staphylococcus aureus (MRSA), vancomycin-resistant bacteria, and non-purulent skin and soft tissue infection (SSTI) in the absence of vasopressors. Data was reported using descriptive statistics and measures of central tendency. Results 167 patients met inclusion criteria with 38.3% from the ICU. SSTIs were most common indication 39 (23.4%) cases, followed by pneumonia and blood with 34 (20.4%) cases each. At time of vancomycin TDM assessment, vancomycin continuation was appropriate 59.3% of the time. Mean of 4.22 ± 2.69 days of appropriate vancomycin use, 2.18 ± 2.47 days of inappropriate use, and total duration 5.42 ± 2.94. 16.4% patients developed an AKI. Majority of missed opportunities were attributed to non-purulent SSTI (28.2%) and missed MRSA nares swabs in 21% pneumonia cases (table 1). Conclusion Vancomycin is used extensively for empiric treatment of presumed infections. Appropriate de-escalation of vancomycin therapy is important to decrease the incidence of adverse effects, decreasing hospital length of stay, and reduce development of resistance. According to the mean duration of inappropriate therapy, there are opportunities for pharmacy and antibiotic stewardship involvement at the time of TDM to optimize patient care (table 1). Missed opportunities for vancomycin de-escalation Disclosures All Authors: No reported disclosures

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Development and Validation of a Method for Quantification of Favipiravir as COVID-19 Management in Spiked Human Plasma

Molecules ◽

10.3390/molecules26133789 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3789

Author(s):

Mohammad Hailat ◽

Israa Al-Ani ◽

Mohammed Hamad ◽

Zainab Zakareia ◽

Wael Abu Dayyih

Keyword(s):

Human Plasma ◽

Internal Standard ◽

Weighting Factor ◽

Hplc Method ◽

Bioanalytical Method Validation ◽

Spiked Human Plasma ◽

Fda Guidance ◽

Significant Difference ◽

Us Fda ◽

Carry Over

In the current work, a simple, economical, accurate, and precise HPLC method with UV detection was developed to quantify Favipiravir (FVIR) in spiked human plasma using acyclovir (ACVR) as an internal standard in the COVID-19 pandemic time. Both FVIR and ACVR were well separated and resolved on the C18 column using the mobile phase blend of methanol:acetonitrile:20 mM phosphate buffer (pH 3.1) in an isocratic mode flow rate of 1 mL/min with a proportion of 30:10:60 %, v/v/v. The detector wavelength was set at 242 nm. Maximum recovery of FVIR and ACVR from plasma was obtained with dichloromethane (DCM) as extracting solvent. The calibration curve was found to be linear in the range of 3.1–60.0 µg/mL with regression coefficient (r2) = 0.9976. However, with acceptable r2, the calibration data’s heteroscedasticity was observed, which was further reduced using weighted linear regression with weighting factor 1/x. Finally, the method was validated concerning sensitivity, accuracy (Inter and Intraday’s % RE and RSD were 0.28, 0.65 and 1.00, 0.12 respectively), precision, recovery (89.99%, 89.09%, and 90.81% for LQC, MQC, and HQC, respectively), stability (% RSD for 30-day were 3.04 and 1.71 for LQC and HQC, respectively at −20 °C), and carry-over US-FDA guidance for Bioanalytical Method Validation for researchers in the COVID-19 pandemic crisis. Furthermore, there was no significant difference for selectivity when evaluated at LLOQ concentration of 3 µg/mL of FVIR and relative to the blank.

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PERFORMANCE CHARACTERISTICS OF A FRET-BASED IMMUNOASSAY FOR QUANTITATION OF INFLIXIMAB ON A POINT-OF-CARE INSTRUMENT SYSTEM

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.135 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S57-S57

Author(s):

Edgar Ong ◽

Ruo Huang ◽

Richard Kirkland ◽

Michael Hale ◽

Larry Mimms

Keyword(s):

Whole Blood ◽

Limit Of Detection ◽

Point Of Care ◽

Quantitative Detection ◽

Therapeutic Drug ◽

Analytical Sensitivity ◽

Sample Type ◽

Hook Effect ◽

Limit Of Quantitation ◽

Assay Precision

Abstract Introduction A fast (<5 min), time-resolved fluorescence resonance energy transfer (FRET)-based immunoassay was developed for the quantitative detection of infliximab (IFX) and biosimilars for use in therapeutic drug monitoring using only 20 µL of fingerstick whole blood or serum at the point-of-care. The Procise IFX assay and ProciseDx analyzer are CE-marked. Studies were performed to characterize analytical performance of the Procise IFX assay on the ProciseDx analyzer. Methods Analytical testing was performed by spiking known amounts of IFX into negative serum and whole blood specimens. Analytical sensitivity was determined using limiting concentrations of IFX. Linearity was determined by testing IFX across the assay range. Hook effect was assessed at IFX concentrations beyond levels expected to be found within a patient. Testing of assay precision, cross-reactivity and potential interfering substances, and biosimilars was performed. The Procise IFX assay was also compared head-to-head with another CE-marked assay: LISA-TRACKER infliximab ELISA test (Theradiag, France). The accuracy of the Procise IFX assay is established through calibrators and controls traceable to the WHO 1st International Standard for Infliximab (NIBSC code: 16/170). Results The Procise IFX assay shows a Limit of Blank, Limit of Detection, and Lower Limit of Quantitation (LLoQ) of 0.1, 0.2, and 1.1 µg/mL in serum and 0.6, 1.1, and 1.7 µg/mL in whole blood, respectively. The linear assay range was determined to be 1.7 to 77.2 µg/mL in serum and whole blood. No hook effect was observed at an IFX concentration of 200 µg/mL as the value reported as “>ULoQ”. Assay precision testing across 20 days with multiple runs and reagent lots showed an intra-assay coefficient of variation (CV) of 2.7%, an inter-assay CV of <2%, and a total CV of 3.4%. The presence of potentially interfering/cross-reacting substances showed minimal impact on assay specificity with %bias within ±8% of control. Testing of biosimilars (infliximab-dyyb and infliximab-abda) showed good recovery. A good correlation to the Theradiag infliximab ELISA was obtained for both serum (slope=1.01; r=0.99) and whole blood (slope=1.01; r=0.98) samples (Figure 1). Conclusion Results indicate that the Procise IFX assay is sensitive, specific, and precise yielding results within 5 minutes from both whole blood and serum without the operator needing to specify sample type. Additionally, it shows very good correlation to a comparator assay that takes several hours and sample manipulation to yield results. This makes the Procise IFX assay ideal for obtaining fast and accurate IFX quantitation, thus allowing for immediate drug level dosing decisions to be made by the physician during patient treatment.

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Quantification of plasma remdesivir and its metabolite GS-441524 using liquid chromatography coupled to tandem mass spectrometry. Application to a Covid-19 treated patient

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0612 ◽

2020 ◽

Vol 58 (9) ◽

pp. 1461-1468 ◽

Cited By ~ 2

Author(s):

Jean-Claude Alvarez ◽

Pierre Moine ◽

Isabelle Etting ◽

Djillali Annane ◽

Islam Amine Larabi

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Half Life ◽

Limit Of Detection ◽

Treated Patient ◽

Internal Standard ◽

Therapeutic Drug ◽

Active Metabolites ◽

Limit Of Quantification ◽

Positive Mode

AbstractObjectivesA method based on liquid chromatography coupled to triple quadrupole mass spectrometry detection using 50 µL of plasma was developed and fully validated for quantification of remdesivir and its active metabolites GS-441524.MethodsA simple protein precipitation was carried out using 75 µL of methanol containing the internal standard (IS) remdesivir-13C6 and 5 µL ZnSO4 1 M. After separation on Kinetex® 2.6 µm Polar C18 100A LC column (100 × 2.1 mm i.d.), both compounds were detected by a mass spectrometer with electrospray ionization in positive mode. The ion transitions used were m/z 603.3 → m/z 200.0 and m/z 229.0 for remdesivir, m/z 292.2 → m/z 173.1 and m/z 147.1 for GS-441524 and m/z 609.3 → m/z 206.0 for remdesivir-13C6.ResultsCalibration curves were linear in the 1–5000 μg/L range for remdesivir and 5–2500 for GS-441524, with limit of detection set at 0.5 and 2 μg/L and limit of quantification at 1 and 5 μg/L, respectively. Precisions evaluated at 2.5, 400 and 4000 μg/L for remdesivir and 12.5, 125, 2000 μg/L for GS-441524 were lower than 14.7% and accuracy was in the [89.6–110.2%] range. A slight matrix effect was observed, compensated by IS. Higher stability of remdesivir and metabolite was observed on NaF-plasma. After 200 mg IV single administration, remdesivir concentration decrease rapidly with a half-life less than 1 h while GS-441524 appeared rapidly and decreased slowly until H24 with a half-life around 12 h.ConclusionsThis method would be useful for therapeutic drug monitoring of these compounds in Covid-19 pandemic.

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Standards of laboratory practice: cardiac drug monitoring

Clinical Chemistry ◽

10.1093/clinchem/44.5.1096 ◽

1998 ◽

Vol 44 (5) ◽

pp. 1096-1109 ◽

Cited By ~ 35

Author(s):

Roland Valdes ◽

Saeed A Jortani ◽

Mihai Gheorghiade

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Drug Monitoring ◽

Free Fraction ◽

Therapeutic Index ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Laboratory Practice ◽

Clinical Complications ◽

The Impact

Abstract In this Standard of Laboratory Practice we recommend guidelines for therapeutic monitoring of cardiac drugs. Cardiac drugs are primarily used for treatment of angina, arrhythmias, and congestive heart failure. Digoxin, used in congestive heart failure, is widely prescribed and therapeutically monitored. Monitoring and use of antiarrhythmics such as disopyramide and lidocaine have been steadily declining. Immunoassay techniques are currently the most popular methods for measuring cardiac drugs. Several reasons make measurement of cardiac drugs in serum important: their narrow therapeutic index, similarity in clinical complications and presentation of under- and overmedicated patients, need for dosage adjustments, and confirmation of patient compliance. Monitoring may also be necessary in other circumstances, such as assessment of acetylator phenotypes. We present recommendations for measuring digoxin, quinidine, procainamide (and N-acetylprocainamide), lidocaine, and flecainide. We discuss guidelines for measuring unbound digoxin in the presence of an antidote (Fab fragments), for characterizing the impact of digoxin-like immunoreactive factor (DLIF) and other cross-reactants on immunoassays, and for monitoring the unbound (free fraction) of drugs that bind to α1-acid glycoprotein. We also discuss logistic, clinical, hospital, and laboratory practice guidelines needed for implementation of a successful therapeutic drug monitoring service for cardiac drugs.

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Therapeutic Drug Monitoring: Psychotropic Drugs

Journal of Pharmacy Practice ◽

10.1177/089719008900200609 ◽

1989 ◽

Vol 2 (6) ◽

pp. 403-415 ◽

Cited By ~ 2

Author(s):

Randall D. Seifert

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Antipsychotic Drugs ◽

Practical Knowledge ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Clinical Use ◽

Careful Patient ◽

Recovery Expectations ◽

Positive Results

The therapeutic monitoring of patients who take antipsychotic drugs can be both challenging and rewarding. Antipsychotics have been in clinical use for over 30 years; yet, their complex pharmacology is not fully understood and parallels our infant knowledge of human brain chemistry. The art of successful therapeutic drug monitoring depends on the clinician's knowledge of basic pharmacology, an understanding of psychiatric disorders, and a sensitivity for careful patient observation. In addition, a thorough history, well thought out goals, and reasonable recovery expectations are essential. Antipsychotic drugs are never curative and should be used judiciously for indications where positive results outweigh the risks of adverse effects. This article will provide the reader with sound, practical knowledge of how to monitor these drugs in any clinical setting. © 1989 by W.B. Saunders Company.

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