Terapeutické monitorování léků umožňuje úpravu dávkování u pacienta na základě stanovení koncentrace léčiva v krvi. Software pro farmakokinetické modelování umožňuje predikovat průběh koncentrací při pravidelném i nepravidelném dávkování, při nestandardních odběrových časech, před dosažením ustáleného stavu nebo při měnící se funkci eliminačních orgánů, zejména ledvin. Příčinou neočekávaných výsledků může být chyba odběru (při odběru ze stejného místa, jako je léčivo aplikováno, nebo odběru z centrálního žilního katétru), neúplná léková anamnéza při změnách dávkování před odběrem, chybějící informace o použití nasycovací dávky, nebo léková interakce. Specifickým případem je podávání léčiva dialyzovaným pacientům, kdy při intermitentní dialýze je nezbytná výrazná redukce dávek, zatímco u kontinuální dialýzy je dávkování úměrné hodnotám sérového kreatininu. Ke správné interpretaci výsledků jsou nezbytné správné a úplné vstupní údaje pacienta a zejména správná dávková anamnéza.
Therapeutic drug monitoring allows the adjustment of the patient's dosage based on the drug concentration. Pharmacokinetic modelling software enables to predict the concentrations with regular and irregular dosing, with non-standard sampling times, before reaching a steady state or with changing function of elimination organs, in particular kidneys. Unexpected results can be caused by a sampling error (esp. when sample was taken from the same site as the drug was administered, or sampling from a central venous catheter), an incomplete drug history during dosage changes before sampling, missing information on the use of a loading dose, or a drug interaction. A specific case is the administration of the drug to dialysis patients, where a significant dose reduction is necessary in intermittent dialysis, while in continuous dialysis the dosage is proportional to serum creatinine values. To correctly interpret the results, correct and complete input data of the patient and, in particular, a full dose history are necessary.
- Keywords
- farmakokinetická analýza,
- MeSH
- Biomarkers, Pharmacological analysis blood MeSH
- Pharmacokinetics MeSH
- Pharmaceutical Preparations analysis administration & dosage blood MeSH
- Humans MeSH
- Drug Monitoring * methods instrumentation statistics & numerical data MeSH
- Specimen Handling MeSH
- Check Tag
- Humans MeSH
- Publication type
- Case Reports MeSH
One of the officially approved medications for the treatment of the pandemic disease COVID-19, caused by the SARS-CoV-2 virus, is remdesivir. This antiviral mole-cule is a prodrug that is metabolized into its active form (an ATP analogue). Because of its hepatotoxicity and ne-phrotoxicity, it is necessary to monitor the serum concen-trations of remdesivir. For the therapeutic drug monitoring of remdesivir, a method using liquid chromatography with tandem mass spectrometry (LC-MS/MS) in positive elec-trospray ionization mode was developed. Mass detection was done via triple quadrupole in the Multiple reaction monitoring mode. Separation was done on Zorbax C18 column at 35 °C in mobile phase gradient and flow 0.4mLmin–1(A –0.1% formic acid in water, B –0.1% formic acid in 95% acetonitrile). Time of analysis was 4minutes. LC-MS/MS method was successfully validated. Calibration was done in blood serum and plasma and it was linear in the range of tested concentrations (0–1000 ngmL–1). Samples were prepared by protein precipitation. The method was used to measure remdesivir concentration in a patient with SARS-CoV-2 infection. The measured concentration 60 minutes after remdesivir application was 175±15 ngmL–1.
- Keywords
- remdesivir,
- MeSH
- Antiviral Agents * analysis pharmacokinetics blood MeSH
- Chromatography, Liquid methods MeSH
- Humans MeSH
- Drug Monitoring methods instrumentation MeSH
- SARS-CoV-2 drug effects MeSH
- Tandem Mass Spectrometry methods MeSH
- Research Design MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Some therapeutic drugs are unstable during sample storage in gel tubes. BD Vacutainer® Barricor™ Plasma Blood Collection Tube with nongel separator was compared with plasma gel tubes, BD Vacutainer PST™, PST II, and BD Vacutainer Serum Tube for acetaminophen, salicylate, digoxin, carbamazepine, phenytoin, valproic acid, and vancomycin during sample storage for up to 7 days. METHODS: Seven hospital sites enrolled 705 participants who were taking at least one selected drug. The study tubes were collected and tested at initial time (0 h), after 48 h of storage at room temperature and on day 7 (after additional 5 days of refrigerated storage). The performance of BD Barricor tube was evaluated for each drug by comparing BD Barricor samples with samples from the other tubes at 0 h from the same participant; stability was evaluated by comparing test results from the same tube at 0 h, 48 h, and 7 days. RESULTS: At 0 h, BD Barricor showed clinically equivalent results for selected therapeutic drugs compared with the other tubes, except phenytoin in BD PST. Phenytoin samples ≥20 µg/mL in BD PST had 10-12% lower values than samples in BD Barricor. During sample storage, all selected drugs remained stable for 7 days in BD Barricor and in serum aliquots. In BD PST, all drugs remained stable except phenytoin and carbamazepine and in BD PST II except for phenytoin. CONCLUSION: The BD Barricor Tube is effective for the collection and storage of plasma blood samples for therapeutic drug monitoring without sample aliquoting.
- MeSH
- Adult MeSH
- Diabetes, Gestational * diagnosis drug therapy MeSH
- Insulin Lispro administration & dosage pharmacology MeSH
- Insulin Infusion Systems MeSH
- Pregnancy Complications MeSH
- Humans MeSH
- Drug Monitoring methods instrumentation MeSH
- Live Birth MeSH
- Blood Glucose Self-Monitoring methods instrumentation MeSH
- Pregnancy MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Keywords
- koagulometr, CoaguChek Pro II,
- MeSH
- International Normalized Ratio MeSH
- Humans MeSH
- Drug Monitoring * methods instrumentation statistics & numerical data MeSH
- Partial Thromboplastin Time MeSH
- Point-of-Care Testing * MeSH
- Prothrombin Time MeSH
- Statistics as Topic MeSH
- Blood Coagulation Tests * methods instrumentation statistics & numerical data MeSH
- Warfarin therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- MeSH
- Diabetes Mellitus, Type 1 * drug therapy metabolism MeSH
- Glycated Hemoglobin standards drug effects MeSH
- Hypoglycemia prevention & control MeSH
- Insulin Glargine administration & dosage MeSH
- Insulin administration & dosage MeSH
- Insulin Infusion Systems standards MeSH
- Humans MeSH
- Drug Monitoring methods instrumentation MeSH
- Blood Glucose Self-Monitoring methods instrumentation MeSH
- Check Tag
- Humans MeSH
Cardiovascular patients take acetylsalicylic acid (ASA) for preventing myocardial infarction and other thromboembolic complications. It is already known that in some patients this therapy is not effective. The aim of this study was to assess the percentage of ASA resistance on the sample of patients with coronary artery bypass grafting. Our study included 105 patients with coronary artery bypass grafting treated with ASA 150 mg/day or lesser. Platelet aggregation was measured by serum thromboxane B2 level as well as impedance aggregometry from whole blood to determine ASA antiaggregation effect. The percentage of ASA resistance was 41.9% with impedance aggregometry, and after determining the serum thromboxane B2 level this percentage was only 8.6%. The correlation between these two methods was weak (r = 0.443; P < 0.0001). Thromboembolic complications still occur in ASA-treated patients because some patients are resistant to ASA therapy. It would be useful to monitor the effectiveness of ASA therapy and give another antiaggregation drug to these patients to reduce adverse events. The problem is which test is ideal because different tests show different percentages of ASA resistance.
- MeSH
- Platelet Aggregation drug effects MeSH
- Aspirin therapeutic use MeSH
- Adult MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Coronary Artery Bypass * MeSH
- Drug Resistance MeSH
- Middle Aged MeSH
- Humans MeSH
- Drug Monitoring instrumentation methods MeSH
- Coronary Artery Disease blood pathology surgery MeSH
- Drug Administration Schedule MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Thromboxane B2 blood MeSH
- Blood Platelets drug effects MeSH
- Platelet Function Tests MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Models based on ordinary differential equations (ODE) are widespread tools for describing dynamical systems. In biomedical sciences, data from each subject can be sparse making difficult to precisely estimate individual parameters by standard non-linear regression but information can often be gained from between-subjects variability. This makes natural the use of mixed-effects models to estimate population parameters. Although the maximum likelihood approach is a valuable option, identifiability issues favour Bayesian approaches which can incorporate prior knowledge in a flexible way. However, the combination of difficulties coming from the ODE system and from the presence of random effects raises a major numerical challenge. Computations can be simplified by making a normal approximation of the posterior to find the maximum of the posterior distribution (MAP). Here we present the NIMROD program (normal approximation inference in models with random effects based on ordinary differential equations) devoted to the MAP estimation in ODE models. We describe the specific implemented features such as convergence criteria and an approximation of the leave-one-out cross-validation to assess the model quality of fit. In pharmacokinetics models, first, we evaluate the properties of this algorithm and compare it with FOCE and MCMC algorithms in simulations. Then, we illustrate NIMROD use on Amprenavir pharmacokinetics data from the PUZZLE clinical trial in HIV infected patients.
- MeSH
- Algorithms MeSH
- Bayes Theorem MeSH
- HIV Infections drug therapy MeSH
- Carbamates pharmacokinetics MeSH
- Clinical Trials as Topic MeSH
- Anti-HIV Agents pharmacokinetics MeSH
- Humans MeSH
- Drug Monitoring instrumentation methods MeSH
- Likelihood Functions MeSH
- Reproducibility of Results MeSH
- Software * MeSH
- Models, Statistical MeSH
- Sulfonamides pharmacokinetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Monitoring, Ambulatory instrumentation MeSH
- Anticoagulants therapeutic use MeSH
- International Normalized Ratio MeSH
- Drug Monitoring instrumentation MeSH
- Prothrombin Time standards MeSH
- Quality Control MeSH
- Blood Coagulation Tests standards instrumentation MeSH
- Point-of-Care Systems standards MeSH
- Equipment and Supplies MeSH
