Sparse sampling (pre-clinical) data

When an NCA model is loaded with the Sparse Sampling option (see “Options tab”), the data are treated as a special case of plasma or urine concentration data. The NCA engine computes the mean concentration or rate at each unique time value or interval. Using the mean concentration curve across subjects, it estimates the same parameters normally calculated for plasma or urine data, plus those listed below. See “Sparse sampling calculation” for additional details of NCA computations with sparse data.

Note:The names of some of the output worksheets change when the data is sparse: Final Parameters becomes Mean Curve Final Parameters, and Summary Table becomes Mean Curve Summary Table.

Plasma or serum concentration parameters

Sparse sampling methods for plasma data (models 200–202) compute the following parameters in addition to those listed in “Plasma or serum data”.

SE_Cmax: Standard error of data at Tmax (time of maximum mean concentration).

SE_AUClast: It is the standard error of the area under the mean concentration curve from dose time to Tlast, where Tlast is the time of last measurable (positive) mean concentration.

SE_AUCall: Standard error of the area under the mean concentration curve from dose time to the final observation time.

Note:SE_AUClast and SE_AUCall provide a measurement of the uncertainty for AUClast and AUCall, respectively, and are usually the same. Differences between these parameter values will only be observed if some of the measurements were flagged as BQL (below the quantitation limit).

Note:With Sparse Sampling, since SE for AUC computations depend on AUC being a linear combination of the mean concentrations, SE_AUClast and SE_AUCall are not included in the output when the output when log trapezoidal rules are specified as the method for computing AUC.

Urine excretion rate parameters

Sparse sampling methods for urine data (models 210–212) compute the following parameters in addition to those listed under “Urine data”.

SE_Max_Rate: Standard error of the data at the time of maximum mean rate.

SE_AURC_last: Standard error of the area under the mean urinary excretion rate curve from dose time through the last interval that has a measurable (positive) mean rate.

SE_AURC_all: Standard error of the area under the mean urinary excretion rate curve from dose time through the final interval.

Individuals by time

This sheet includes the individual subject data, along with N (number of non-missing observations), the mean and standard error for each unique time value (plasma data) or unique midpoint value (urine data).

References

Holder (2001). Comments on Nedelman and Jia's extension of Satterthwaite's approximation applied to pharmacokinetics. J Biopharm Stat 11(1-2):75–9.

Nedelman, Gibiansky and Lau (1995). Applying Bailer's method for AUC intervals to sparse sampling. Pharm Res 12:124–8.

Nedelman and Jia (1998). An extension of Satterthwaite's approximation applied to pharmacokinetics. J Biopharm Stat 8(2):317–28.

Yeh (1990). Estimation and Significant Tests of Area Under the Curve Derived from Incomplete Blood Sampling. ASA Proceedings of the Biopharmaceutical Section 74–81.