D-propoxyphene: Accumulation or altered kinetics?

Wa, Colburn; Ce, Inturrisi

doi:10.1007/bf00607926

Cited by 3 publications

(2 citation statements)

References 3 publications

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“…More important is patient management: the time lost for a patient, who is not responsive to treatment, can be significantly reduced. A biomarker that substitutes a clinical endpoint is called a surrogate endpoint [30][31][32][33]. The most important criteria for valid surrogates are biological plausibility, a documented statistical relationship between the surrogate and an accepted clinical endpoint in epidemiological studies, and demonstration that treatment effects on the surrogate correspond to the clinical outcome.…”

Section: E Clinical Studiesmentioning

confidence: 99%

In Vivo magnetic resonance techniques and drug discovery

Beckmann¹

2006

Braz. J. Phys.

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The long and resource intensive process of drug discovery and development is confronted with the basic challenge of providing effective and safe therapies at reasonably low costs. The better the mechanism of a disease is known, the higher the probability to find an appropriate therapy. Also, the better and earlier a disease can be diagnosed and characterized, the higher the chance to be able to interfere in this process with a chemical entity. This reasoning sets the framework for the use of imaging in drug discovery. We discuss the relevance of magnetic resonance imaging and spectroscopy to derive anatomical, functional, metabolic and target-related information in the context of pharmacological research in vivo.

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Section: E Clinical Studiesmentioning

confidence: 99%

In Vivo magnetic resonance techniques and drug discovery

Beckmann¹

2006

Braz. J. Phys.

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“…Over a decade ago, both industry ( Colburn 2000 ) and regulators ( Food and Drug Administration 2004 ) recognized that a new approach, taking advantage of advances in scientific and technical methods, was needed to improve efficiency along the path from laboratory concept to commercial product. The approval of 45 new drugs in 2015, the highest number approved since 53 were approved in 1996 ( Mullard 2016 ), indicates that this new approach may be having an impact.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Imaging in Pharmaceutical Development and Its Impact on the 3Rs

Campbell

Trotter

Hines

et al. 2016

ILAR J

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It is well understood that the biopharmaceutical industry must improve efficiency along the path from laboratory concept to commercial product. In vivo imaging is recognized as a useful method to provide biomarkers for target engagement, treatment response, safety, and mechanism of action. Imaging biomarkers have the potential to inform the selection of drugs that are more likely to be safe and effective. Most of the imaging modalities for biopharmaceutical research are translatable to the clinic. In vivo imaging does not require removal of tissue to provide biomarkers, thus reducing the number of valuable preclinical subjects required for a study. Longitudinal imaging allows for quantitative intra-subject comparisons, enhancing statistical power, and further reducing the number of subjects needed for the evaluation of treatment effects in animal models. The noninvasive nature of in vivo imaging also provides a valuable approach to alleviate or minimize potential pain, suffering or distress.

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Assessment of Drug Accumulation in the Evaluation of Pharmacokinetic Data

Meineke

Gleiter

1998

The Journal of Clinical Pharma

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The evaluation of drug accumulation is approached from a practical point of view. Estimates of accumulation indices as obtained from standard estimators-AUC, peak levels, and trough levels (RAUAUC Rmax and Rmin, respectively)-are compared and differences analyzed. The estimators are based on the concentration-time curve characteristics area under the concentration-time curve (AUC), maximum concentration, and trough level. Simulated data are used for the analysis, both noise-free and with random error added. The data are based on pharmacokinetic parameters derived from a clinical study. The numerical procedures can be reproduced by the interested reader with little effort. It is shown empirically that if Rmin, > RAUC then simple kinetic behavior cannot be safely assumed, but accumulation is a complex function of time. Rmax as obtained from the data and an estimate of this value based on time to peak concentration (tmax) and apparent elimination rate constant (lambda(z)) after a single dose and at steady state can then be compared in an attempt to exclude time-dependent kinetics. This new numerical procedure can provide valuable and even pivotal information regarding the accumulation kinetics of a compound under investigation. Recommendations on how to use the available concentration-time information to the best advantage are presented. It is concluded that the assessment of drug accumulation should not be confined to the calculation of just one estimate, because the three estimators RAUC, Rmax. and Rmin reflect different aspects of accumulation. Moreover, all information about accumulation should be carefully analyzed in the clinical context. This way the relevant accumulation can be identified for safe and efficacious drug treatment.

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D-propoxyphene: Accumulation or altered kinetics?

Cited by 3 publications

References 3 publications

In Vivo magnetic resonance techniques and drug discovery

In Vivo magnetic resonance techniques and drug discovery

In Vivo Imaging in Pharmaceutical Development and Its Impact on the 3Rs

Assessment of Drug Accumulation in the Evaluation of Pharmacokinetic Data

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