Testing for the equality of area under the curves when using destructive measurement techniques

Bailer, A. John

doi:10.1007/bf01062139

Cited by 302 publications

(206 citation statements)

References 6 publications

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“…Hence to permit statistical comparison of the AUC between groups, the Bailer's method was used. α was set at 0.05 and critical value of Z (Zcrit) for a two sided test was adjusted at 2.24.The Z value calculated as mentioned previously (2).…”

Section: Discussionmentioning

confidence: 99%

The Single Dose Poloxamer 407 Model of Hyperlipidemia; Systemic Effects on Lipids Assessed Using Pharmacokinetic Methods, and its Effects on Adipokines

Chaudhary

Brocks

2013

J Pharm Pharm Sci

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-Purpose:The induction of hyperlipidemia using poloxamer 407 (P407) is gaining use for studying the effect of the condition on drug pharmacokinetics. Although a single intraperitoneal dose of P407 causes a rapid onset of hyperlipidemia, the initial lipid concentrations are much higher than seen in humans. The hyperlipidemia is also reversible in nature. Here, pharmacokinetic methods were used to assess the P407 dose response on serum lipids, adipokines and cytokines. Methods: Single 0.5 and 1 g/kg doses of P407 were injected into rats followed by blood collection at various times for up to 12 d. Serum was assayed for lipids, selected adipokines and cytokines. Results: As expected, large increases in lipid levels were seen by 36 h after dosing. Using area under the concentration vs. time curve as a measure of systemic lipid exposure, P407 increased serum baseline corrected serum lipids in a nearly dose proportional fashion. The maximum increase in lipids was observed at ~36 h, with most lipids remaining elevated for up to ~180 h, although for the 1 g/kg dose triglyceride concentrations had still not quite returned to baseline by 12 days postdose. In addition to changes in lipids, P407 significantly increased serum leptin and decreased the serum adiponectin concentrations but did not affect cytokine levels. Conclusion: Depending on study aims, for the use of the model it may be beneficial to perform single-dose assessments at time points later than 36 h when the lipoprotein concentrations will be more similar to those seen in patient with hyperlipidemia.

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Section: Discussionmentioning

confidence: 99%

The Single Dose Poloxamer 407 Model of Hyperlipidemia; Systemic Effects on Lipids Assessed Using Pharmacokinetic Methods, and its Effects on Adipokines

Chaudhary

Brocks

2013

J Pharm Pharm Sci

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“…Pharmacokinetic Studies: The mean AUC 0→Tlast estimated for each study group after administration of treatment were compared using Bailer's method [23].…”

Section: -8 Statistical Analysismentioning

confidence: 99%

Disposition of everolimus in mdr1a−/1b− mice and after a pre-treatment of lapatinib in Swiss mice

Chu¹,

Abbara²,

Noël-Hudson³

et al. 2009

Biochemical Pharmacology

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“…Furthermore, all of the calculated pharmacokinetic parameters were similar whether the compounds were dosed alone or in combination. Statistical analysis, using the method of Bailer (61,62), revealed that there were no significant differences between the dose-normalized AUCs of the compounds following cassette and single compound administration. In this case, the results obtained from in vitro metabolic stability studies did not reflect the in vivo pharmacokinetics of these compounds.…”

Section: Dmpk In Drug Discoverymentioning

confidence: 99%

The application of cassette dosing for pharmacokinetic screening in small-molecule cancer drug discovery

Smith

Raynaud

Workman

2007

Molecular Cancer Therapeutics

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Pharmacokinetic evaluation is an essential component of drug discovery and should be conducted early in the process so that those compounds with the best chance of success are prioritized and progressed. However, pharmacokinetic analysis has become a serious bottleneck during the 'hit-to-lead' and lead optimization phases due to the availability of new targets and the large numbers of compounds resulting from advances in synthesis and screening technologies. Cassette dosing, which involves the simultaneous administration of several compounds to a single animal followed by rapid sample analysis by liquid chromatography/tandem mass spectrometry, was developed to increase the throughput of in vivo pharmacokinetic screening. Although cassette dosing is advantageous in terms of resources and throughput, there are possible complications associated with this approach, such as the potential for compound interactions. Following an overview of the cassette dosing literature, this article focuses on the application of the technique in anticancer drug discovery. Specific examples are discussed, including the evaluation of cassette dosing to assess pharmacokinetic properties in the development of cyclin-dependent kinase and heat shock protein 90 inhibitors. Subject to critical analysis and validation in each case, the use of cassette dosing is recommended in appropriate chemical series to enhance the efficiency of drug discovery and reduce animal usage. [Mol Cancer Ther 2007;6(2):428 -40]

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Testing for the equality of area under the curves when using destructive measurement techniques

Cited by 302 publications

References 6 publications

The Single Dose Poloxamer 407 Model of Hyperlipidemia; Systemic Effects on Lipids Assessed Using Pharmacokinetic Methods, and its Effects on Adipokines

The Single Dose Poloxamer 407 Model of Hyperlipidemia; Systemic Effects on Lipids Assessed Using Pharmacokinetic Methods, and its Effects on Adipokines

Disposition of everolimus in mdr1a−/1b− mice and after a pre-treatment of lapatinib in Swiss mice

The application of cassette dosing for pharmacokinetic screening in small-molecule cancer drug discovery

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