Abstract
The concept of a weighted pool for estimating the area under the curve (AUC) is presented and set in relationship to the trapezoidal rule. An example from a pharmacokinetic study on ethinyl estradiol is used to demonstrate the use of variance component analysis for relating the intraindividual variance of the AUC, trapezoidal rule and weighted pool to the variance of the determination process. Depending on the sampling times, the theoretical variance of the weighted pool is greater than the theoretical variance of the trapezoidal rule. In the example presented, it was shown that this difference is of no importance in relation to the interindividual variance of the AUC, which dominates the total variance. In the example study, routine quality control samples were also determined in each assay, which allowed independent confirmation of the discussed results on the intraindividual variance of the AUCs.
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Dibbelt L, Knuppen R, Juetting G, Heimann S, Klipping C, Parikka-Olexik H (1991) Group comparison of serum ethinyl estradiol, SHBG and CBG levels in 83 women using two low-dose combination oral contraceptives for three months. Contraception 43: 1–21
Jung-Hoffmann C, Kuhl H (1989) Interaction with the pharmacokinetics of ethinylestradiol and progestrogens contained in oral contraceptives. Contraception 40: 299–312
Huempel M, Taeuber U, Kuhnz W, Pfeffer M, Brill K, Heithecker R, Louton T, Steinberg B (1990) Comparison of serum ethinyl estradiol, sex-hormone-binding globulin, corticoid-binding globulin and cortisol levels in women using two low-dose combined oral contraceptives. Horm Res 33: 35–39
Scheffé H (1959) The analysis of variance. Wiley, New New
Yeh K C, Kwan KC (1978) A comparison of numerical integrating algorithms by trapezoidal, Lagrange, and spline approximation. J Pharmacokinet Biopharm 6: 79–98
Bailer AJ, Piegorsch WW (1990) Estimating integrals using quadrature methods with an application in pharmacokinetics. Biometrics 46: 1201–1211
Gallicaano KD, Mc Gilveray IJ, Qureshi S, Nitchuk W, Chakraborty B, Boyd C (1991) Situation paper: comparative bioavailability of oral contraceptive products. Clin Biochem 24: 107–111
Kuhnz W, Hümpel M, Schütt B, Louton T, Steinberg B, Gansau C (1990) Relative bioavailability of ethinyl estradiol from two different oral contraceptive formulations after single oral administration to 18 women in an intraindividual cross-over design. Horm Res 33: 40–44
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Louton, T., Kuhnz, W., Dibbelt, L. et al. Weighted serum pools in comparison to the trapezoidal rule for estimating AUCs for ethinyl estradiol. Eur J Clin Pharmacol 46, 77–81 (1994). https://doi.org/10.1007/BF00195920
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DOI: https://doi.org/10.1007/BF00195920