BlueBerry is a web software with a graphical user interface that has a goal of providing a standard Moment analysis module on the Internet. Since this is a web-based software, we are trying to make it available on various environments (e.g., operating systems and devices). This document will be updated as the software updated.
We are actively listening to you. Please leave your comments on this page or send an email directly to the developers if there is any concern about BlueBerry. Comments are always welcome, and the software will be continuously improved. The updates would be shared with the update history. We hope this software, released with good intentions, is helpful. However, there is no warranty for the results that this software produce and the software itself. Please, use this software from a critical viewpoint based on the pharmacokinetic knowledge you have, and please let us know if there is any concern, again.
This page is printable. This guide is based on the BlueBerry 2021.07.25 update.
This section introduces the environment for developing and testing this program currently. In the environment written here, we are trying to support all possible features. However, in the case of mobile devices, there may be some limitations. We are trying to make all features available on a fixed device such as a PC or laptop.
The support environment below will change according to the latest environment over time.
You can use BlueBerry by accessing https://nca.simcube.org/blueberry. If the address is changed, the URL would be automatically redirected to the changed address.
Click the Add Data button at the top of the list page.
Select the data you want to see on the list page (https://nca.simcube.org/blueberry). There will be the result values (e.g., half-life, clearance, and volume of distribution), graphs, etc. analyzed through moment analysis.
The structure of the data view page address is https://nca.simcube.org/blueberry/data:[data number]@[data creator ID]. Data can be accessed only by the creator of the data or by those authorized to be shared.
We are developing a data sharing function, and when the sharing function is applied, we plan to make it available to attach data on your posts so that you can share your opinions. Access rights to data are reserved by the data creator or those designated by the data creator. Through future development, we plan to allow authors to specify permissions for specific groups.
Entered data can be corrected. You can edit the entered data by clicking the "Edit" button at the bottom of the view page. Automatically calculated values cannot be modified.
The structure of the data editing page address is https://nca.simcube.org/blueberry/nca/data:[data number]@[data creator ID]. The right to modify the data is held by the data creator or the person designated by the data creator.
The entered data is automatically analyzed according to the information entered by the data creator.
If the units entered for dose do not match the units entered for concentrations, the prefix is interpreted as follows to match the two units.
International unit prefix (SI Prefix)
|SI Prefix||Scientific Notation|
PK parameters are calculated based on the input data. The formula for each parameter is as follows. Significant digits indicated when calculating parameters are unified to 4 digits. These significant figures are rounded up and displayed at the very end of the calculation process, and the most accurate mathematical constants that can be obtained in a 64-bit system were used for the calculation. However, since we did not receive information about the significant digits of the number entered, it does not mean information about the actual significant digits. Please consider the significant digits that are meaningful for your data.
Outputs the dose entered by the user. When used for calculation, it is used after unit conversion. If entered in mol-based unit, it can be calculated after converting to gram using the molecular weight.
It means the concentration at the time zero (0). Blueberry will estimate the concentration at the time zero for a single dose, and at the time of the last administration for repeated doses. If there are other inputs from the user, an estimate is obtained according to the following rules:
There are three interpolation methods to choose from for calculating AUC and AUMC. If you choose the log-trapezoidal method, the interval where the concentration increases over time is still calculated according to the linear-trapezoidal method.
Calculates the area under the curve of the concentration-time curve from time 0 to the last observation time based on the interpolation method you selected. However, if you selected the log-trapezoidal formula, if two concentrations have the same value in an interval, or if one of the values is not positive, the linear-trapezoidal formula is used to calculate that interval.
Calculate the area under the curve (AUC) of the concentration-time curve from time 0 to infinity. Extrapolate by assuming that the concentration after the concentration at the time of the last observation decreases as a single exponential function. Do not calculate if λZ is negative (when the concentration in the terminal phase increases with time).
Indicates the percentage extrapolated when calculating the AUC.
For repeated doses, calculates the area under the concentration-time curve from the time of the last dose to τ. The calculation method depends on the selected interpolation method.
Calculates the area under the curve of the concentration-(time*time) curve from time 0 to the last observation based on the interpolation method you selected. However, if the log-trapezoidal formula is selected and the two concentrations are equal or non-positive in an interval, the area under the curve for that interval is calculated using the linear-trapezoidal formula.
Calculate the area under the curve of the concentration-(time*time) curve from time 0 to time infinity. Concentrations after the concentration at the time of the last observation are extrapolated by assuming that the concentration-time curve follows an exponential function. If λZ is negative (the concentration of the terminal phase increases with time), it is not extrapolated to the time infinity.
Indicates the extrapolated ratio when calculating AUMC.
In the case of repeated administration, the area under the curve of the concentration-(time*time) curve from the time of the last administration to τ is calculated. The calculation method depends on the selected interpolation method.
Calculate systemic clearance.
For extravascular route data, since AUC includes bioavailability (F), it is calculated as:
For repeated dose data, CLss is calculated because steady state is assumed.
If the input data is repeated dose, AUCτ and AUMCτ would be calculated. In the case of single dose, AUC and AUMC would be calculated and utilized for the further estimation. In the case of extravascular input, The value of MRT will contain mean absorption time (or mean input time).
If the data indicates IV infusion, 주입 시간을 고려하여 계산합니다. Tin은 주입 시간을 의미합니다.
Estimated mean residence time calculated by the concentration from zero to the last sampling time.
The volume of distribution at steady-state. This will be calculated only in the case of IV bolus injection and continuous IV infusion because estimated MRT after extravascular input (e.g., oral administration) will contain the time delay by absorption and the mathmatical formula below cannot estimate the Vss.
The volume of distribution based on terminal phase.
The steady-state will be assumed for the repeated dose, and the volume (VZ or VZ/F) will be calculated by below:
In the case of repeated dose, the ratio of accumulated concentration by steady state will be estimated by below:
The slope of terminal phase. This parameter will be estimated by a linear regression of log-transformed concentration over time plot. The range of terminal phase will be determined by the biggest Adjusted R2, but the higher number of observation for terminal phase will be selected if the difference of Adjusted R2 is smaller than 0.0001 among the comparison. The range before Tmax will not be included in the terminal phase. In the case of infusion, the observed concentrations during the infusion time will not be included in the terminal phase. If the data is not after IV bolus input, Tmax will not be included in the terminal phase.
At least three observation which is acceptable for the critera above is needed for the terminal phase estimation.
If the concentration increases during the terminal phase, λZ will not be estimated.
The terminal phase half-life.
The number of observations in the terminal phase which is selected by the method above (see section λZ).
The squared Pearson correlation coefficient for the estimation of λZ. The R2 will be calculated in the log-transformed concentration-time profiles.
This parameter is calculated for the selection of the number of terminal phase. The Adjusted R2 is calculated because the R2 has tendency to become higher in the more number of observations.
The averaged concentration at the steady state.