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which lumen of the catheter is used to take a sample of blood for TDM? the same of where the drug was administered?
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Fully agree with Mark's response. For example, a four-lumen central venous catheter could be used to delivery drug, CVP monitoring and draw blood sample. Following the industry's recommendation, the distal lumen for CVP monitoring as minimal impact by vessel wall, and the proximal lumen for drawing blood sample as minimal impact by the delivering drug.
hope it is helpful.
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Thanks to give me information about the necessity of ethical code for these types of cohort projects
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yes
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1. Is there a need to monitor blood levels of clozapine and it's metabolite when the doses are low and no serious adverse effects are occurring?
2. If there are consensus guidelines on TDM for clozapine I cannot find them. Please point me in the right direction.
Thanks
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A review of the clinical utility of serum clozapine and norclozapine levels
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I'm doing the population pharmacokinetics modelling with a Tacrolimus database and I found out that in some patients, there is a period of 5 days without administration, (for ex, at time after dose: 0, 12, 24, 36, 48, 60, the corresponding concentration was 17, 14.5, 14, 10.5, 8.7, 7.3). 
As we cannot verify the source of information and I do not have real clinical experience with this drug, I wonder is it possible to have this kind of kinetics (that the drug remained very long in the patient body) or we can assume that there is maybe some dose that was not recorded?
If by chance anyone has looked at/ modelled real-life TDM data of tacrolimus, can you please share your opinion?
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if in the toxic range, first order kinetics may change to zero order kinetics, or indeed drug/drug interactions should be considered 
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I'm doing the population pharmacokinetics modelling with a Tacrolimus database and I found out that in some patients, there is a period of 5 days without administration, (for ex, at time after dose: 0, 12, 24, 36, 48, 60, the corresponding concentration was 17, 14.5, 14, 10.5, 8.7, 7.3).
As we cannot verify the source of information and I do not have real clinical experience with this drug, I wonder is it possible to have this kind of kinetics (that the drug remained very long in the patient body) or we can assume that there is maybe some dose that was not recorded?
If by chance anyone has looked at/ modelled real-life TDM data of tacrolimus, can you please share your opinion?
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Well, in fact, the terminal half-life is the same for extended and immediate release forms it depends on the clearance of the drug (when TAC is in the body this TAC whether it has been administered as extended or immediate release form) which can be modulated by hepatic function alteration and drug interactions for instance. The PK profile you display can be seen in patients with a decrease clearance. Once again, this can be attributed to a CYP3A4/5 inhibitor comedication or a decrease in hepatic function.
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Therapeutic drug monitoring of concentrations of drugs in body fluids, usually plasma, can be used during treatment and for diagnostic purposes. The selection of drugs for therapeutic drug monitoring is important as the concentrations of many drugs are not clearly related to their effects.
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If there isn't a clear dose dependent effect or the medication is thought to have a reliable pharmacokinetic profile drug level monitoring may not be recommended.  Furhter medications that are titrated to effect may be better monitored by effectiveness than drug level, lastly some medications like levodopa, patients have a variable response so one drug level may not be effective for another patient, hope this helps
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I found it in the review paper by Miura and Takahashi (2015) Routine therapeutic drug monitoring of tyrosine kinase inhibitors … (table 1). The first example: LOQ above the lowest concentration level - method linear in a range of 25-2500 ng/mL, the LOQ 30 ng/mL. The second example: LOQ below the linearity reange – method linear in a range of 100 – 10000 ng/mL, the LOQ 50 ng/mL.
I checked the original publications. The data in the Table 1 are correct. The LLOQ values were calculated using the equation LOQ=Standard Deviation/Slope of the calibration curve. Requirements of FDA and EMA describe the LLOQ as the lowest calibration standard. According to this the sensitivity of the mentioned methods should be 30 ng/ and 100 ng/mL, respectively. Is it correct?
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In accordance with the metrological definition of sensitivity – see e.g. JCGM 200:2012 – analytical sensitivity is simply the slope of the calibration curve. Thus the linearity range is characterized by a constant sensitivity, which is not affected by the Limit of Quantification.
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I would like to use Morisky scale to measure adherence and compare the result with therapeutic drug monitoring .There is a validated Arabic version of morisky scale so if I get the copyrights from prof. Morisky should I
1. conduct pilot study ?what is the sample
2. conduct Construct validity
3. test-retest reliability
4. Known group validity
5. Sensitivity and specificity
And after that I compare with therapeutic drug monitoring or no
thank you
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This scale is copyright protected,permission is required
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rhIL-11 seems to be widely used in China for Chemotherapy-Induced Thrombocytopenia, but some papers I read demonstrate that rhIL-11 has limited use because of its side effect, I'd like to know how it is used outside China. is thereany one to help?
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I don't have experience with rhIL-11 (Oprelvekin) because it is not available in Thailand (Non-Thai FDA Approval) from the literature dose 50 mcg/kg Sc once daily 10-21 days. The side effects quite different from GCSF, such as hypersensitivity reactions, fluid retention, arrhythmia and anemia. But I familiar with eltrombopag and romiplostim the efficacy of these agents are difficult to evaluate, our physicians use in many cases with heavily chemotherapy treatment. And need to check drug-drug interaction and platelet count closely.
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Paracetamol suppositories made with PEG 4000 and PEG 6000 as suppository bases undergo dissolution test. After 45 minutes, both batches have mean % of drug release that is higher than 100%.
PEG 4000- 150% and PEG 6000- 120%
Why does the cumulative drug release exceed 100%? Is there error during measuring of absorbance or is it some form of degradation or hydrolysis of the medicine during manufacture/storage?
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Dear Ahmed,
Polymorphs are solid state-of-matter crystal forms? But, for an assay you're dealing with a solution. So the specific absorbance (in solution) will be identical, no matter which polymorph dissolved. You may be thinking of mutorotation, but the assay is by absorbance, not optical rotation.
Rachel, paracetamol is stable in the body until metabolized, which processes usually don't involve attack at the phenol group. So it's likely to be comparably stable once in solution in a dissolution test. As to the possible attack by PEG impurities, you might see http://www.spectra-analysis.com/documents/AppNote016Polyethyleneglycol.pdf , with the caveat that the sample had been "vigorously air oxidized" (hot?). Consider that PEG is used in many preparations, and that it may block chemical carcinogenesis, both of which wouldn't be practical if it generated large amounts of peroxides. I do note that sonication (to disperse or dissolve solids in a solution or semisolid) may degrade PEG, see https://en.wikipedia.org/wiki/Polyethylene_glycol . So don't do that!
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I am looking for literature, which shows the influence of adding organic solvent to whole blood in order to perform sample preparation followed by centrifugation. I would need quantitative information of which solvent in which ratio as well as the relation of G number (of the centrifugation) and duration applied to whole blood in order to precipitate all proteins on to separate them. All papers tend to use high G numbers and a quite short time, but what happens if you use a lower G value for a longer time and what's the difference of using methanol or acetonitrile in a ratio of 1:3 or 1:5. Does anyone know a proper reference which investigated this issue systematically? We are looking for small molecules (metabolites) and pharmaceuticals in whole blood and want to get a minimum of residue protein in the solution by using an optimum G number and duration for centrifugation. Currently our capabilities of centrifugation are limited.
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Well, I agree about using the given centrifuge at the maximum anyway. Regarding the equippen I have at the moment, I wonder whats the difference between 1, 2, 10 or 30 minutes at 1300 g or 3000 g. And how this compares with I centrigugation at 20'200 g for 3 or more minutes. Of course I will have to test it under our extraxtion conditions, but it would be nice to have some specific litature, which shows some values I could compare with. Like size of the particles and residual protein (a bit like in the paper you showed me, but depending ion the certifugation parameters).
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There is the specific interaction between target cells and therapeutic agents. I am focussing on the determination of possible cellular targets of therapeutic peptides. I think MS and RNAseq analysis could be applied in this. Please give me suitable protocols and idea and efficacy in addressing my question.
Are there other methods to address the above question? Please suggest me and give some explanation.
Thank you.
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Dear BiveK,
I would definitely recommend MS. By MS you can identify specific proteins that are highly expressed in you cancer cell lines, or even directly compare the MS spectrum between the cancer cell lines and normal cell lines. After identifying these possible peptides you would proceed with tandem MS to determine the specific sequence of each of the previously identified peptides. 
Here is some relevant literature in the matter:
Protein Sequencing and Identification Using Tandem Mass Spectrometry by Michael Kinter and Nicholas E. Sherman, Wiley
Teen and Mann (2004) The ABC’s (and XYZ’s) of peptide sequencing. Nature Reviews 5:699-711.
Kellie et al. (2010) The emerging process of top down mass spectrometry for protein analysis: biomarkers, protein-therapeutics, and achieving high throughput. Mol Biosyst. 6:1532-1539.
Hope this helps you,
Best,
Rita Pedrosa
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I have developed bioanalytical method for estimation of Lamotrigine in human plasma using LC-MS/MS and now I am going to apply my method to Therapeutic drug monitoring and Pharmacokinetics in epileptic patients.
I had already taken 3 patients blood samples at different time interval and done the same analysis by LC-MS/MS.
Now, the problem is whatever Lamotrigine concentarions getting from the patients sample analysis was too high, it was out from the my linearity range upto 30- 40 times. I had taken blood samples at 0, 0.5, 1,2,3,4, 12 and  24 hrs from patients.
Patient dose profile:
drug given
Lamictal 100mg ....... 1---0---1
so, what can i do....for better analysis?
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Kashyap.
You could dilute your samples with the same matrix your method was validated. You could validate the dilution process, may be in several concentration level, if you thinks necessary.
For calculate the final concentration of samples, you use the dilution factor.
Another way is validate your method in another linear range. But will require more time.
I hope  help you.
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Can anyone suggest how to measure meclofenamic acid (MFA) concentration in blood or in retinal tissue?
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C = Dose/Vd
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There is evidence showing that monitoring drug concentration during HAART is generally not necessary. Several RCTs found limited benefits among patients with TDM compared with those without TDM. However, it is known that low drug concentration is directly associated with virologic failure. What's more, during one of our studies, we found that people with a low drug concentration for the first 12 weeks would benefit if they could elevate their concentration later (those who elevated their concentration had lower viral failure rate). We think that TDM is necessary for patients. And we wonder whether previous RCTs made full use of their TDM data. Did the physicians provide sufficient help to increase patients adherence?
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TDM could help in monitoring adherence to treatment in hiv/aids treatment
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For example, an ixabepilone dose is 40 mg/m2 and the maximum dose is 88mg based on a BSA of 2.2 m2. Therefore, if a person's BSA is 2.5, the dose is capped at 88mg instead of 100mg.
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Thank you for your response. But I'm still puzzled by why 2.2 and not some other number. Is there any pharmacokinetic study out there that reports capping the BSA at 2.2 reduces toxicity in obese patients?
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I am looking for the release parameters of Microtrol beads for Adderall XR so that I may include absorption rate or rate constants in a pharmacokinetic model of Adderall XR. Can you describe the kinetics or provide references?
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Yes. This will be helpful for not only there is some useful content but the names may be useful if I can establish the contacts. Thank you Fakhrul.
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Is there anyone who can tell me about a free web-based calculator or app (or spreadsheet) to determine the time in therapeutic range for warfarin?
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I have just downloaded it and haven't tried it yet. I have a home-made one also in an Excel sheet but it is a little bit cumbersome to use.
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Resistance to antibiotics is the most common factor these days, if the patient develops resistant to high class antibiotics what would be the alternate therapy?? Is it necessary to continue the same to act against gram negative bacteria, in case of third generation cephalosporins?? Please help me in finding the positive and negative prospects assigned with the antibiotic therapy?
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The answer to your question depends on many factors, first of all why the third generation cephalosporin was prescribed. Which type of infection and what bacteria are suspected. Second you should clarify better what you mean by a patient develop resistance (during a therapy course or he come back to the physician with a relapse?).
Usually it is unlikely to develop resistance during the therapy, but is more likely that the patient is already infected with resistant strains (you will see it by noting that after an initial improvement in the patient conditions there will be a worsenings after a few days).
In any case, depending on the suspected infectious agents, the doctor may switch to another anti gram-negative drug or an anti MRSA drug, or even an anti anaerobic drug as add on therapy. These are the bacterial infections that are not covered by third generation cephalosporins, i.e. multidrug resistant gram negatives, MRSA and anaerobes. This is true for the majority ofcases but of course as usual there are exceptions.
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Comment
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Eye movement desensitization and reprocessing
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The trough serum levels of the pharmacologically active metabolite of a drug often follow lognormal distribution in a population even when the distribution of the serum levels of the parent drug show the Gaussian pattern. I would like to find out what the underlying mathematical reasons and the pharmacokinetic mechanisms of this phenomenon are.
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The assumption that drug concentrations (trough, peak, active metabolite, etc.) may be described by a log normal distribution is based on pragmatic considerations.
True concentrations (but not necessarily measurements) must be non-negative i.e. they could be zero or positive. The normal distribution always includes negative concentrations so it is a priori not suitable. The log normal distribution is always positive so it is a better assumption than the normal. Of course it fails to describe the most common situation which occurs when the true concentration is zero (the most common situation is not to be taking the drug that is being studied!).
But in the special case when a particular drug is known to have been ingested then the assumption that the true conc is zero becomes very unlikely. So the log normal assumption is often used based on pragmatism. It is certainly not based on biological or pharmacokinetic theory.
Note that a more sensible assumption is that the distribution of concentrations must also account for the dosing history and other fixed effects such as weight, age, disease state, drug interactions, etc. This is the usual way the distribution of concentrations is modelled.
The residual error of a measurement (not the true concentration - please try to understand the difference between the truth and a measurement) can usually be best described by a combination of a log normal distribution and a normal distribution. The normal distribution part describes the background error process and this can be negative, zero, or positive. This is perhaps the most common assumption made by pharmacokineticists who are aware of the sources of residual error in measurements of drug concentration.
The assumption that the residual error of measured concentrations is only log normally distributed is quite often made when analysing observed data. But this assumption leads to the foolish conclusion that all drug concentrations should be measured as late as possible after the dose if a formal optimal design process is used to design a PK study. The background error should never be forgotten when trying to describe measurements.
Nick