Interpretation of unreplicated two-level factorial experiments, by examples

Sundberg, Rolf

doi:10.1016/0169-7439(93)e0041-2

Cited by 22 publications

(11 citation statements)

References 4 publications

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“…Haloperidol (Janssen-Cilag, Beerse, Belgium) was found to be a suitable internal standard and could be safely used in this medication-free population. A two-level factorial experimental design [14] was applied to the solid-phase extraction with two dierent types of extraction columns, Isolute HCX and Isolute PH (International Sorbent Technology Ltd., Mid Glamorgan, UK), respectively. Both columns gave an acceptable yield for the metabolite, but only the Isolute PH column gave satisfactory results for the internal standard and was therefore used.…”

Section: Methodsmentioning

confidence: 99%

“…After evaporation at 40°C, the samples were redissolved in 300 ll mobile phase, and 50 ll was injected on the HPLC. Applying the two-level factorial experimental design [14] to the HPLC separation resulted in a separation on a 3.9´150 mm C8 Symmetry column (Waters Chromatography, Milford, Mass., USA). The mobile phase consisted of 0.085 M KH 2 PO 4 buer (pH 4.5)/acetonitrile/methanol (74.3:20:5.7 v/v/v).…”

Section: Methodsmentioning

confidence: 99%

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The major fluvoxamine metabolite in urine is formed by CYP2D6

Spigset¹,

Axelsson²,

Norström³

et al. 2001

Eur J Clin Pharmacol

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Objective: Previous studies have shown that uvoxamine is metabolized by CYP1A2 and CYP2D6, but there is no information on the impact the various CYP enzymes have on the dierent metabolic pathways of¯uvoxamine biotransformation. The present study was designed to investigate this issue. Methods: The major¯uvoxamine metabolite, the 5-demethoxylated carboxylic acid metabolite, was analyzed in urine from 50 healthy volunteers after intake of a single oral dose of 50 mg¯uvoxamine, and the formation clearance for the metabolite (CL m ) was calculated. Of the subjects, 28 were non-smoking CYP2D6 and CYP2C19 extensive metabolizers (EMs), 12 were smokers and were thus considered to have an induced CYP1A2 activity, 5 were CYP2D6 poor metabolizers (PMs), and 5 were CYP2C19 PMs. In 11 of the nonsmoking EMs, 200 mg caeine was given at another occasion in order to calculate oral caeine clearance as a measure of CYP1A2 activity. In addition, CL m was calculated in ten other subjects given increasing doses of uvoxamine for 4 weeks. Results: Oral clearance of¯uvoxamine was signi®cantly higher in smokers, and signi®cantly lower in CYP2D6 PMs than in non-smoking EMs. CL m was 78% lower in CYP2D6 PMs than in the EMs. Smoking and being a CYP2C19 PM did not in¯uence CL m . There was no signi®cant correlation between oral caeine clearance and CL m . CL m decreased with increasing¯uvoxamine dosage, but the decrease in oral clearance was even higher. Conclusion:These results indicate that CYP2D6 catalyzes the major metabolic pathway of¯uvoxamine, whereas CYP1A2 seems to catalyze other less important pathways. Both the CYP2D6 and the CYP1A2 pathways seem to be saturated in parallel with increasinḡ uvoxamine dosage.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The major fluvoxamine metabolite in urine is formed by CYP2D6

Spigset¹,

Axelsson²,

Norström³

et al. 2001

Eur J Clin Pharmacol

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“…The literature about outlier detection and identification in factorial experiments [17][18][19][20][21] was of limited use in this case. It is based on the redundancy of higher order effect estimates, which is not equivalent with the sparsity of effects in a main effects model.…”

Section: Concluding Discussionmentioning

confidence: 99%

A classical dataset from Williams, and its role in the study of supersaturated designs

Sundberg

2008

Journal of Chemometrics

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A Plackett-Burman type dataset from a paper by Williams [1], with 28 observations and 24 two-level factors, has become a standard dataset for illustrating construction (by halving) of supersaturated designs (SSDs) and for a corresponding data analysis. The aim here is to point out that for several reasons this is an unfortunate situation. The original paper by Williams contains several errors and misprints. Some are in the design matrix, which will here be reconstructed, but worse is an outlier in the response values, which can be observed when data are plotted against the dominating factor. In addition, the data should better be analysed on log-scale than on original scale. The implications of the outlier for SSD analysis are drastic, and it will be concluded that the data should be used for this purpose only if the outlier is properly treated (omitted or modified).

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“…This means that the result can be described as a function based on the experimental variables [2] , Y= (f) x. The function (f) x. is approximated by a polynomial function and represents a good description of the relationship between the experimental variables and the responses within a limited experimental domain.…”

Section: Empirical Modelsmentioning

confidence: 99%

General Introduction to Design of Experiments (DOE)

Eldin¹

2011

Wide Spectra of Quality Control

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Interpretation of unreplicated two-level factorial experiments, by examples

Cited by 22 publications

References 4 publications

The major fluvoxamine metabolite in urine is formed by CYP2D6

The major fluvoxamine metabolite in urine is formed by CYP2D6

A classical dataset from Williams, and its role in the study of supersaturated designs

General Introduction to Design of Experiments (DOE)

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