The design of pharmacokinetic experiments for model discrimination

Lacey, Laurence; Dunne, Adrian

doi:10.1007/bf01061725

Cited by 10 publications

(6 citation statements)

References 12 publications

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“…These designs generally replicate the p sampling points, where p is the number of parameters estimated. Clearly, this type of design is quite different from that described by Lacey & Dunne (1984).…”

Section: Non-linear Modelsmentioning

confidence: 88%

Statistical analysis of pharmacokinetic data

Powers

1990

Vet Pharm & Therapeutics

102

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Section: Non-linear Modelsmentioning

confidence: 88%

Statistical analysis of pharmacokinetic data

Powers

1990

Vet Pharm & Therapeutics

102

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“…[26][27][28][29] To demonstrate the usefulness of these algorithms, computer simulations have been performed to demonstrate the improvements to reaction modeling for a myriad of applications. [30][31][32][33][34][35][36] Incorporation of these techniques with experimental data are less reported, but applications include hydrogenation 37 and crystallization. 38 The experimental designs in these applications were developed before data collection.…”

Section: ' Introductionmentioning

confidence: 99%

Rapid Determination of Reaction Kinetics with an Automated Microfluidic System

McMullen

Jensen

2011

Org. Process Res. Dev.

162

132

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Kinetic information is used to determine the optimal reaction conditions, to successfully scale up a reaction from the laboratory to the pilot plant, and to improve process control. Obtaining accurate kinetics using conventional benchtop equipment and techniques, however, requires numerous experiments and can be complicated by sluggish mixing and heat-transfer rates. To improve the speed and efficiency in gathering reaction kinetics, we present an automated, silicon microreactor system that uses a sequential experimentation framework driven by model-based optimization feedback for online reaction rate parameter determination. The method, based on Information Theory and Bayesian Statistics, first selects the appropriate global reaction rate expression. After determining the correct rate law, a D-optimal strategy precisely estimates the pre-exponential and activation energy of the rate constant. The approaches are validated experimentally with a model system, the Diels−Alder reaction of isoprene and maleic anhydride in DMF. The benefits of quickly obtaining this information with an automated microreactor system are further demonstrated by successfully scaling the Diels−Alder reaction by a factor of 500 from a microreactor to a Corning flow reactor.

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“…Following the application of an appropriate procedure for curve fitting, the model must be selected by the use of objective mathematical techniques (Lacey & Dunne 1984;Yamaoka et al 1978). It is possible that final analysis of the data in all individuals may not yield uniform agreement regarding model selection when a drug is given at different dose levels or when complete data sets are available for analysis.…”

Section: Standard Pharmacokinetic Techniquesmentioning

confidence: 99%

Paediatric Labelling Requirements

Wilson

Kearns

Murphy

et al. 1994

Clinical Pharmacokinetics

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The US Food and Drug Administration (FDA) has proposed new labelling regulations that describe alternative approaches for providing additional information to support labelling a drug, already approved for use in adults, for use in children. Therefore, the study of drugs in paediatric populations may now be encouraged. Paediatric pharmacokinetic studies are an important part of these trials. This action by the FDA may help resolve the ethical and technological concerns about the performance of clinical trials in children, and may render paediatric clinical trials more feasible. Most investigations in children are opportunistic in nature and their design is often constrained by a requisite noninvasive approach. Appropriately applied population-based techniques for both pharmacokinetic and pharmacodynamic data analysis may represent the most robust approach for generating a sufficiently large and accurate database for the use of new or old drugs in paediatric patients. Accordingly, this information, which is crucial for paediatric labelling of any drug product, must be obtained in infants and children if we are to truly individualize therapy for paediatric patients. The funding of 6 Pediatric Pharmacology Research Units by the US National Institutes of Health, and guidelines for application of pharmacokinetic methods to children may further contribute to the performance of paediatric clinical trials.

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The design of pharmacokinetic experiments for model discrimination

Cited by 10 publications

References 12 publications

Statistical analysis of pharmacokinetic data

Statistical analysis of pharmacokinetic data

Rapid Determination of Reaction Kinetics with an Automated Microfluidic System

Paediatric Labelling Requirements

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