Do non-compartmental analysis on a single-dose set of concentration vs. time data
calc_nca(time, conc, detect, series_id = NULL, dose, route, method = "z", ...)A `data.frame` with 9 rows and `length(method) + 3` variables. See Details.
A numeric vector of time points.
A numeric vector of concentrations. If detected (above limit of detection/quantification), contains the measured value; if not detected (below LOD/LOQ), contains the LOD/LOQ.
A logical vector: Whether each concentration was detected (above LOD/LOQ) or not.
Optional: A variable that can be coerced to a factor, identifying individual time series (e.g., individual replicates -- individual subjects, or replicate dose groups). Default NULL, in which case each observation will be assumed to have a different series ID. In other words, a serial sampling design will be assumed, in which each observation is from a different subject.
A numeric scalar: The dose for this data set.
A character scalar: The route of administration for this data set. Currently, only "oral" and "iv" are supported.
As for [PK::nca()]: the method to use for calculation of confidence intervals. Default `'z'` (this differs from the [PK::nca()] default).
Other arguments that will be passed to [PK::nca()] (other than `data`, `design`, and `method`: *i.e.*, `n.tail`, `nsample`)
Caroline Ring
This function is a wrapper around [PK::nca()] to do non-compartmental analysis, after automatically detecting the study design. It additionally calls [get_peak()] to calculate the peak concentration and time of peak concentration.
# Automatic detection of study design
[PK::nca()] understands three different study designs, and requires the user to specify which one is being used.
- `ssd`: Serial sampling design. Each observation is from a different subject. - `complete`: Every subject was observed at every time point. - `batch`: Each subject was observed at multiple time points, but not at every time point.
To automatically detect which study design is applicable, this function first sorts the data by increasing time. Then, a table of time vs. series ID is created, with 1 indicating that a measurement exists for the corresponding time point/series ID combination, and 0 indicating that a measurement does not exist. If the column sums of this table are all 1, then it is a serial sampling design, except if there is only one observation per time point, it is a complete sampling design, and if there are multiple observations for some time points and only one observation for other time points, it is a batch design. If the column sums are all equal to the number of rows of the table, then it is a complete sampling design. Otherwise, it is a batch sampling design.
# Parameters estimated by NCA
- `AUC_infinity`: The area under the concentration-time curve, extrapolated out to infinite time. Estimated using the trapezoidal rule, with a tail area correction calculated using the slope of the last 3 data points (by default). - `AUC_tlast`: The area under the concentration-time curve, calculated at the last observed time point. Estimated using the trapezoidal rule. - `AUMC_infinity`: The area under the concentration-time first moment curve (the area under the AUC vs. time), extrapolated out to infinite time. Estimated using the trapezoidal rule, with a tail area correction calculated using the slope of the last 3 data points (by default). - `CLtot`: The total clearance rate. Only calculated for `route == 'iv'`. If `route == 'oral'`, this is `NA_real_`, and only `CLtot/Fgutabs` is calculated. - `CLtot/Fgutabs`: The total clearance rate, normalized by the oral bioavailability. Only calculated for `route == 'oral'`. If `route == 'iv'`, this is `NA_real_`, and only `CLtot/` is calculated. - `Cmax`: The peak concentration. For `route == 'iv'`, this is expected to be the concentration at the earliest time; for `route == 'oral'`, it is not. This and `tmax` are calculated using [get_peak()], not by [PK::nca()]. - `halflife`: The half-life of elimination. Only calculated for `route == 'iv'`. If `route == 'oral'`, this is `NA_real_`, because half-life estimates are not valid for oral data. - `MRT`: The mean residence time. Only calculated for `route == 'iv'`. If `route == 'oral'`, this is `NA_real_`, and only `MTT` is calculated. - `MTT`: The mean transit time (the sum of MRT and mean absorption time). Only calculated for `route == 'oral'`. If `route == 'iv'`, this is `NA_real_`, and only `MRT` is calculated. -`tmax`: The time of peak concentration. For `route == 'iv'`, this is expected to be the earliest time; for `route == 'oral'`, it is not. This and `Cmax` are calculated using [get_peak()], not by [PK::nca()]. - `Vss`: The volume of distribution at steady state (`AUMC_infinity/AUC_infinity^2`). If `route == 'oral'`, this is `NA_real_`, because `Vss` estimates are not valid for oral data.
# Output
The output is a data.frame with 9 rows (one for each NCA parameter) and a number of variables equal to `length(method) + 3`.
The variables are
- `design`: The automatically-detected design. One of `ssd`, `complete`, or `batch` (or `NA_character_` if no analysis could be done). - `param_name`: The name of each NCA parameter. - `param_value`: The value of each NCA parameter. - `param_sd_[method]`: The parameter standard error estimated by the corresponding method.