Pharmacokinetics - Science topic
Pharmacokinetics are dynamic and kinetic mechanisms of exogenous chemical and drug ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and TOXICOLOGY as a function of dosage, and rate of METABOLISM. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. ADME and ADMET are short-hand abbreviations for absorption, distribution, metabolism, elimination and toxicology.
Questions related to Pharmacokinetics
my work on molecular docking, pharmacokinetics, DFT
Does somebody has a pharmacokinetics model available in Excel? I’m working with a lot medications and would very much like to know how it builds up and to what extent. A simple model suffices but assume that multiple administration is required. Thanks very much, Marcel
Dear Kinetic experts,
I need one kind suggestion from you. One X compound with molecular weight of 200.1, is highly water soluble with oral bio-availability of 65-75%. In that case I want to achieve 1 micro mole in plasma (irrespective to protein bound %) for that how much dose I should give by orally. Is that any standard formula is available for this calculation?
Please note that in my study design, if the compound reaches more than 1.5 micro mole it will become inactive. So specific concentration in plasma is really challenge. Please help with this
In the article titled "FDOPA-(18F): a PET radiopharmaceutical recently registered for diagnostic use in countries of the European Union", two half-lives are reported for FDOPA.
"6-fluoro-(18F)-L-dopa is removed according to a bi-exponential kinetic process with biological half-lives of 12 hours (67-94 %) and 1.7 - 3.9 hours (6-33 %). Both these half-lives appear to be age-dependent. The 18F-activity is excreted through the kidneys, 50 % with a half-life of 0.7 hours and 50 % with a half-life of 12 hours.
On basis of these data, a biokinetic model for 6-fluoro-(18F)-L-dopa was developed. This model assumes that 100 % of the 18F activity is homogeneously distributed in the body and eliminated through the kidneys with biological half-lives of 1 hour (50 %) and 12 hours (50 %). This model was considered to be independent of age."
What does this mean?
Someone was taking Daflon 500 mg (450 mg Diosmin, 50 mg Hesperidin) twice daily for her varicose veins. Now, the manufacturer makes Daflon 1000 mg (900 mg Diosmin, 100 mg Hesperidin).
Now, the Q is, if she takes the new dosage form 1000 mg once daily, will this dose be equivalent to 500 mg once daily or the pharmacokinetics and the therapeutic effects will be different?
I have some synthesized drug and want to study the pharmacokinetic of this drug. But I am confused with the dosing calculation, how much dose i should administer to animal especially rat for the evaluation of pharmacokinetic evaluatioion.
Most free webservers that I am using for predicting the pharmacokinetics and biological activities of molecules are restricted to organic molecules only not exceeding over 1,200 in molecular weights. However, there are interesting biomolecules in nature that deserve attention for in silico studies which cannot be tested using these online tools.
Times 0.5, 1, 2, 4, 6 hours and concentrations <2.50, <2.50, 7.80, 53.3, 279
I am using PKsolver the excel add in but I am not getting the expected value.
I have 4 groups, each group is composed of 5 mice, I set up to withdraw at 7 intervals to complete my study. It is not possible to withdraw 7 samples from a single mouse so Is it scientifically right to withdraw 3-4 samples from all group members (5 mice) on a triplicate base and then calculate PK parameters, average them and calculate SD? Is that acceptable scientifically?
I'm working on my master degree i'm measuring peak plasma concentrations for a drug (cmax) and will correlate it with a genetic marker but i made a mistake of not fixing a time interval for blood samples withdrawals i drawed the samples within a time range
Is there a way that i can use to correct real sampling times so i can use it and correlate it with the genetic marker
''Using the pharmacokinetic parameters and a pharmacokinetic-pharmacodynamic model, it is possible to predict the pharmacodynamic response to certain drugs; this provides useful information for understanding drug action and determining dosage regimen''. (Baggot, 1990)
Baggot JD. Pharmacokinetic-pharmacodynamic relationship. Ann Rech Vet. 1990;21 Suppl 1:29S-40S.
Simple pharmacokinetic parameters of five potent compounds after a single oral administration to female mice.
how to review this pharmacokinetic results
Is it possible to determine the correction factor (Km) to estimate the (AED) for Lepidopteran species? Haven't found any literature that discusses the MRSD for Lepidopteran species. Would very much appreciate it if someone has any insight into it. Need to calculate the drug dose for Bombyx Mori.
Did you ever experience a conceptual change in pharmacology where was a discrimination b/w phenomena/concepts that you previously regarded as a single phenomena/concept?
For instance, proton pump inhibitors are often thought to be interchangeable, but some differences have emerged in their pharmacological properties, which may be reflected in some aspects of clinical efficacy. Such differences include potency, speed of onset and duration of pH 'holding times' (2004)
Robinson M. Review article: the pharmacodynamics and pharmacokinetics of proton pump inhibitors--overview and clinical implications. Aliment Pharmacol Ther. 2004;20 Suppl 6:1-10. doi:10.1111/j.1365-2036.2004.02160.x
needing help in the criteria of choosing the drug to use when studying pharmacokinetics changes in patients with congestive heart failure
As we know, polymyxin B contains many components (e.g. polymyxin B1, B2, etc.), do we have any evidence to show that those major components have different antimicrobial activity, pharmacokinetic property and propensity for toxicity?
Simcor contains simvastatin and niacin. Simvastatin is metabolized by CYP3A4, and niacin is able to inhibit this isoform. Is niacin a strong or weak CYP3A4 inhibitor? Can niacin alter simvastatin pharmacokinetics?
In the pharmacokinetics and pharmacodynamics of frusemide
I have data for concentration vs time for plasma and other tissues of the body for orally administered drug. I got analysis for plasma only using PK solver (Microsoft excel based Add-in) but not for other tissues.
I am having trouble interpreting some pharmacokinetic data. I work with mice. I have two groups of animals all given with the same drug in the same route at the same dosage. There were statistically significant differences in the AUC, Clearance, and Cmax between groups. However, the half-life was the same for all groups. Two of these groups were infected with a virus that replicates in the kidneys, so we expected them to have impaired renal clearance of the drug. If that were the case, wouldn't we see a prolonged t1/2? I am concerned that even though there are differences in the AUC and Clearance, without changes in T1/2, we can't conclude that the variation in PK parameters is due to changes in renal function.
Is there any software available to simulate the behaviour (growth, differentiation etc.) of different cell type on an implant surface.
Also, software related to simulation of drug loading and release from a drug carrier and its pharmacokinetics.
I have harvested urine and serum at various time intervals from rats that have been given a crude extract . I want to assess the pharmacokinetics and pharmacodynamics of the individual compounds in the extract. However, I am not sure which method will work better for the pharmacokinetics because I do not know the proportion of each of the compounds in the extract.
I am trying to evaluate PK profile (Plasma vs. time) of Test compounds in ICR mouse after PO administration as a screening study.
The common PK profile of these drugs indicates IV pattern, despite oral administration.
The meaning of the IV pattern that i mentioned is that the concentration of durgs in the plasma continuously decreases from first sampling time point (5 min) to the last sampling time point (24h).
In general, When administered with PO, it takes time for the drug to be absorbed, indicating a pattern in which the drug slowly increases and decreases.
When the drug is absorbed quickly after PO administration,
Can it indicate IV pattern?
Please give me advice
I am injecting intrathecally (between L5-L6) , in rats, cannabinoid analgesics and I was wondering if they can reach the brain and have effects there as well ?
Also I need to pretreat with antagonists (AM630 and Capsazepine) and was wondering how long does it take to get them cleared from spinal cord. I usually pretreat for 30min before agonist injections, is this too long or is it ok ? (we are interested in spinal effects only). I cannot inject the agonist and the antagonist simultaneously as the volume of each injection is too big to inject them one after the other (I had to dilute drugs in bigger volume in order to lower % of ethanol of solution: 20uL for antagonist and 30uL for agonist)
Nonlinear mixed-effects models (may) consider data below the limit of quantification (BLQ) in parameter estimation. However, an evaluation of the goodness-of-fit plots (observations vs predictions in particular, using spline interpolation), displays a strong trend (of spline interpolation, but not of the data) in the region of censored data, as if the model disregarded BLQ data and the data were the lower limit of quantification itself, as structured in the database. I believe that the database is structured correctly and that the model considered the censored interval. Apparently this plot is the only one to exhibit this behavior.
Is spline interpolation adequately representing the competence/capability of the final model in this case? How to handle this situation?
I want more information about role of chiral drugs on drug delivery based on pharmacology, pharmacokinetics, pharmacodynamics, recepter binding, dose, potency , toxicity, safety with lot of examples. If you have any reference materials like article, book, or other formats and you please send to me.
Currently working on a new drug, previously tested on cell culture studies only. Will administer through IP injection. How do I assess its permeability into the brain and across the bbb? Thanks.
I have to study the pharmacokinetics of floating sustained-release tablets in rats. I have read about the research article regarding the same. But they did not mention clearly, what type of assembly was used for the dosing of the mini-tablets (unbreakable) in rats. I am looking for a clear idea regarding the assemble and procedure of dosing used during the study.
Thank you in advance.
I came across with this study here, https://www.clinexprheumatol.org/abstract.asp?a=5066
And this study says: "The sample size calculation was done to compare two different MTX starting dose regimens, based on a study investigating the pharmacokinetics of 25 mg of methotrexate (22) assuming a 67% higher MTX level in the accelerated dose regime and a dose-proportional bioavailability. We calculated that 9 patients in each dosing group will be sufficient to detect the expected difference in the pharmacokinetics of methotrexate (α=0.05, β=0.80)."
Any idea of what formula that they are using to come up with the 9 sample size?
I want to establish the correlation between in vitro dissolution profile with in vivo pharmackinetic profile. Can any one please tell me how i can establish in vitro in vivo correlation (IVIVC)?
I have in vitro dissolution data for generic drug and I want to predict in vivo pharmacokinetics parameters, please suggest me free software tools or high quality R packages that can achieve this. Also please share suitable keywords I can use to search on this topic other than In- Vitro In Vivo Correlation (IVIVC)!
Can Microsoft Excel be used instead of the popular NONMEM for population pharmacokinetics?
When I viewed the PK parameters of both warfarin and candesartan, I found that both medications have 99% plasma protein binding. I then went to check and confirm there will be PK interaction through resources and I was surprised when I found no interaction! So can it be? Any explanation?
Is there any reference/Book/Software that shows only the pharmacokinetic parameters of all medications available? For example, if I want to know the absorption, metabolism of acetaminophen, I should open the monograph in this reference and see all the information I need, the same goes for omeprazole, cetirizine, any medication. Is there such a resource/reference?
I would like to plan a treatment regime with subcutaneous administrations, but I have only spare pharmacokinetic literature data on the compound I use in my experiments. Most of the data are from IV administrations, and I am wondering, which of the followin parameters can I use to estimate pharmacokinetics of the same compound after subcutaneous administration?
- volume of distribution
- elimination rate constant and half-life
- What is the time taken for steady state to be established in adults for ( Mycophenolate mofetil ) ?
how can i collect many blood sample from the rat for pharmacokinetic study without killing the rat??
I can fathom the idea of PK being different b/w dogs and rodents, but why would I be seeing a significantly different PK profile for the same drug tested on rats and mice?
I am interested in soaking a drug in a gel foam and then applying the foam topically in vivo to try to obtain a more sustained release of the compound. Do you have any experience with this please? Pros / Cons?
Is it necessary to construct the calibration curve of the drug in plasma for in-vivo pharmacokinetic study? Can we use simple calibration curve of drug constructed in solvent not in the plasma matrix, for quantification of the drug in plasma samples?
If comparing formulations of curcumin reported in the literature, which are also available commercially, by their Cmax values, if they have all used different doses, is it scientifically appropriate to dose-normalise each Cmax to say 100mg and then compare their bioavailability that way?
Could you compare liposomes with micelles in this way, native to micelles etc
Please suggest the name of software freely available online for calculation of pharmacokinetic parameters
I found in some of the articles that the Cmax and Tmax of Test and standard to be the same in the pharmacokinetic study but in our experiment both Cmax and Tmax of test were found to be increased as compared to standard. Is our result ok????Please suggest.
I am interested on the general opinion regarding how transferrable/comparable are the Km/Vmax values for membrane transporters obtained for example in vitro using transfected cells and ex vivo (such as isolated membranes) or in situ (perfusion studies).
If anybody has a good paper to send me on the topic, I'd really appreciate it.
Thank you in advance!
We are currently trying to create a hepatocyte clearance method that can be used for compounds which are slowly cleared. To do this we are plating the hepatocytes on collagen 48-well plates (viability prior to plating determined using trypan blue). We allow the cells to adhere for 6 hours, change the media, leave the plates overnight and then the next day carry on with metabolic competency studies over a 24 hour period. The hepatocytes we use are these and we follow the supplier instructions: https://www.thermofisher.com/order/catalog/product/WICP10?SID=srch-srp-WICP10#/WICP10?SID=srch-srp-WICP10
While we are carrying out the metabolic competency studies we would like to determine how viable the cells are over the 24 hour period. We initially thought to use CellTiter Glo however, it doesn't seem as though it is lysing all of the cells in the well. We use CellTiter Glo according the the suppliers instructions - take the plate out allow it to equilibrate for 30 minutes at room temperature, add the CellTiter Glo in a 1:1 ratio and shake the plate at 90RPM for 30 minutes before measuring luminescence.
Manual for CellTiter Glo: https://ch.promega.com/-/media/files/resources/protocols/technical-bulletins/0/celltiter-glo-luminescent-cell-viability-assay-protocol.pdf
We were wondering if we could maybe add an additional lysis buffer alongside CellTiter Glo? To see whether that would help in fully lysing the cells over the 30 minute period. I've also read some papers online which talk about measuring Caspase 3 activity or Lactate Dehydrogenase... Wondered if anyone could shed some light?
I am a new researcher so please excuse my lack of experience..
Thank you :)
I would like to do some transport assays using tissue from mice that I have experimentally perturbed
Trying to engage the wits of my fellow compatriots on this platform to seek online resources that provides free learning opportunities on fundamentals for PK. Looking for something like coursera that can be a self-learning source providing beginner to advanced training. Should be free!
I have the invitro and cell based invitro concentration of a molecule . But I am struggling with deciding the concentrations that should be screened in mice for the pharmacokinetic study of the molecule. How can we extrapolate the invitro data for setting up invivo experiments?
I am aware this is a rather odd question but I couldn’t find any answers to this in the literature. One study has used sperm cells as a drug delivery tool (see below) but I was wondering if it might have broader implications. Would sperm injected into the bloodstream survive for long? What about if it was taken orally? Would appreciate any thoughts!
May I know what is an acceptable R-square value for modelling of drug release kinetics?
I have fitted my experimental data for drug release to first order (gastric simulation) and Korsmeyer-Peppas (buccal cavity). The R-square values obtained are in the range of 0.85 - 0.99.
There are numerous articles about development of various chitosan-based nanoparticles for parenteral drug/gene/vaccine delivery but I was unsuccessful to find any references about the pharmacokinetics of these nanoparticles. Are they degradable inside cell endosomes? Could such nanoparticles ever be eliminated from the organism after parenteral administration?
I am working on pharmacokinetic studies , and trying to find out the plasma drug concentration and facing trouble in this . can anyone help me how you estimate drug concentration from plasma??
What's the difference between food and drug kinetics in human body?
I'd like to estimate drug plasma concentrations at a specific time. All participants were patients using a benzodiazepine chronically. The equation I want to use is included in the attachment, but whenever I fill it out I end up with ridiculously high plasma concentrations. I was hoping someone could show me how to fill in the equation using the example case below:
Body weight= 60kg; Temazepam 20mg oral administration of hard capsule every 24 hours; Last administration is 3 hours before testing; F=0.96; Vd= 1.4L/kg; Cl= 1.19L/min/kg; Ka= 0.35; Kel= 0.05
I've conducted a trial where I have administered a drug through several routes, including IV. I have plasma concentrations at various time-points.
Now I'm trying to find a program that can help me calculate the half-life of elimination and absorption, and the bioavailability. Any suggestions as to what software to use?
I have the values of all pharmacokinetics parameters for both the reference and test formulations. How can I calculate the effects of formulation, period, sequence and subjects from these parameters?
I injected two injections into rats via tail vein, irinotecan injection and an herbal extract injection-A (composed of Astragalus membranaceus extract, ginseng extract and oxymatrine). Group1 received only irinotecan; Group2 received a mixture of irinotecan and A; Group3 received A first, and irinotecan was injected 15 minutes later. The injection volume of each group and the concentration of irinotecan in each group were the same. The data demonstrated that at 5 minutes after injection, there was no difference in the plasma concentration of irinotecan between group 3 and group 1, while the plasma concentration of group 2 was increased about 5 times compared to group 1, and AUC was also significantly increased. I analyzed the concentration of irinotecan before and after mixing of the two injections in vitro, no difference. The change in pH after mixing also did not cause too much conversion of lactone and carboxylate forms of irinotecan (lactone forms still accounts for the majority). So why did the injection of a mixture of irinotecan and another drug increase the rat plasma concentration of irinotecan?
Is there any pharmacokinetics data for metoprolol tartrate (Cmax) and its solubility?
I want pharmacokinetic data (Plasma conc. vs time) of certain drugs to build physiologically based pharmacokinetics models. How can I find such data for the studies listed in clinicaltrials.gov? In the results sections, only the pharmacokinetic parameters extracted from that data is given.
I need to calculate the AUC of serum DHA over 28 days. The follow-up for the DHA measurement was expected to be on baseline, day 2, day 5, day 10, day 15, and day 28. It is very possible that some of the participants will not come at exactly the same schedule day. For example, some come at day 26 and some come at day 29. I am planning to calculate the AUC with trapezoidal method. In this case, how should I handle different follow-up time?
i am study a bio distribution for free drug and its conjugated metabolites in different organs in rat , i constructed a calibration curve and HPLC method analysis for free drug and i couldn't do the same because i don't have pure standards for metabolites owing to its high price ,
My question is : Can i explain the bio-distribution for free drug and its metabolites as a ratio between their AUCs following non linear regression based on their absorbance on HPLC ? or it is scientifically wrong
Thank you in advance
Ministry of AYUSH and other guidelines
Firstly, thanks a lot for your kind contribution.
We are interested in identifying how aging could influence pharmacokinetics in humans. To do so, we are planning to create/modify human cell lines which could translate the human aging to a certain extent. After that, We will study how different aged cells influence the pharmacokinetics of a particular drug.
P.S. I have checked earlier threads but could not find the right match.
I want to see a list of the most widely used PK/PD software (pharmacokinetic) that is used by big pharma and biotech.
I am currently using methanol for lysis of plated cells (in 96-well plate), in order to quantify the concentration of substrate within the cells.
However, I am not sure if methanol is very efficient in the lysis since i still observe many cells still attached to the surface. Also, methanol also evaporate very quickly, and this will add variability into my experiment.
Is methanol a good choice or there are other alternatives available?
(Lysis buffer is not suitable as I am using LC/MS for quantification.)
I am analyzing PK data by 2 compartment model. %CV is much lower using 1/Y^2 weighting. However, I am not sure if this is the right way. Can anybody suggest what criteria I need to follow for 2 compartment model.
In NCA, we get 2 volumes of distribution: Vz (elimination) and Vss (steady state). Which one would be the actual volume of distribution.
If you know any articles that report the pharmacokinetic properties and bioavailability of ip CNO injection (1mg/kg) in the brain, please let me know ! Thanks in advance
I have seen in many cases of clinical trials, oncologists give colony stimulating factors with the treatment .. do they change pk parameters, how likely it is to affect data ?
I would be greatly appreciated if anyone can provide me with some information about the physio-chemical, pharmacokinetics, and toxicological properties of Altholactone.
Thanks in advance.
If someone has been taking Candesartan 4 mg one tablet daily for a year and want to take Diclofenac 25 mg for occassional pain, How can I eliminate the interaction between both (Aside from monitoring blood pressure and renal function)? Is there a way where I can separate the interaction. I read that half life of diclofenac is 2 hours so can he take Candesartan after 2 hours from ingesting Diclofenac or it (Candesartan) already in the blood as he has been taking it for a year, so the interaction will inevitably occur?