Maximum Tolerated Dose of Nalmefene in Patients Receiving Epidural Fentanyl and Dilute Bupivacaine for Postoperative Analgesia

Dougherty, Thomas B.; Porche, Vivian H.; Thall, Peter F.

doi:10.1097/00000542-200004000-00018

Cited by 24 publications

(18 citation statements)

References 6 publications

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“…Selective -and k-agonists were differentiated in this neuroendocrine biomarker by apparent pK B analysis with the clinically available antagonist, nalmefene (Negus et al 1993;Wang et al 1998;Dougherty et al 2000;Bowen et al 2002). Thus, the nalmefene apparent pK B value for the -agonist fentanyl was significantly higher than for the k-agonist spiradoline (France and Gerak 1994).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the discriminative and neuroendocrine effects of centrally penetrating κ-opioid agonists in rhesus monkeys

2002

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Section: Discussionmentioning

confidence: 99%

Comparison of the discriminative and neuroendocrine effects of centrally penetrating κ-opioid agonists in rhesus monkeys

2002

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“…Adult anesthesia examples of CRM include determining the optimal volume of 1% lidocaine for adductor canal block , the ED 95 dose for 0.5% bupivacaine for ultrasound‐guided supraclavicular block , the ED 95 of prilocaine for femoral nerve block using ultrasound , or the maximum tolerated dose of nalmefene in patients receiving epidural fentanyl and dilute bupivacaine for postoperative analgesia .…”

Section: Sequential Design Methodsmentioning

confidence: 99%

Sequential allocation trial design in anesthesia: an introduction to methods, modeling, and clinical applications

Görges

Zhou

Brant

et al. 2017

Pediatric Anesthesia

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Summary Estimation of the dose–response curve for new anesthetic protocols typically focuses on identifying minimum effective doses. The application of a sequential experimental method is appropriate, as it minimizes sample size requirements by updating dose assignments based on information accrued from successive subjects. One approach is the up‐and‐down method for estimating the median effective dose in a patient population (ED50). Designs better suited for achieving greater than 50% effectiveness, include the biased coin approach, and continual reassessment method. In this review we introduce different sequential design methods, provide examples of their use, and show through simulation how the method employed influences sample size and the accuracy of the estimated dose. Simulation studies are presented to illustrate the effects of dose parameter and stopping rule choice for up‐and‐down method and biased coin approach. For continual reassessment method, the effects of assumed dose–response model, prior guess, and cohort size are simulated. A binary response regression curve was fit to the data in Saidman and Eger's endtidal halothane dose‐finding study to provide a dose–response curve for generating simulations. A range of options exist when designing a study using sequential allocation with biased coin approach or continual reassessment method. Method choice influences the required sample size and confidence in estimated effect. In the halothane example, up‐and‐down method decreases the required sample size by 20–30% when the choice of design parameters is optimal. For both up‐and‐down method and biased coin approach designs, greater sample sizes, arising from adjusted stopping criteria, might be required to achieve reliable estimates. The continual reassessment method is only efficient if a limited range of doses can be chosen a priori. In conclusion the up‐and‐down method can be more efficient than nonsequential designs for the estimation of the median dose/intervention level for a given intervention (ED50). The biased coin approach or continual reassessment method are preferred for the estimation of higher or lower tail quantiles such as ED90 or ED10. Continual reassessment method may be superior if knowledge of the dose–response relationship is available for the drug of interest.

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“…For example, Dougherty et al [2000] applied the CRM in a study to establish the MTD of Nalmefene that spared analgesia in a subset of patients for postoperative pain control. Similarly, Desfrere et al [2005] applied the CRM to determine the minimum effective dose of intravenous ibuprofen required to close ductus arteriosus.…”

Section: Oncology Phase I Types Of Dose Findingmentioning

confidence: 99%

Adaptivity in drug discovery and development

Bretz

Branson

Burman

et al. 2009

Drug Development Research

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The development of novel drugs is becoming increasingly challenging, inefficient, and costly, as acknowledged by all major stakeholders of pharmaceutical products. Adaptive designs have attracted considerable attention in recent years, as they promise an increase in efficiency of the drug development process by making better use of the observed data. The key idea of adaptive designs is to use data accumulating from an ongoing experiment to decide on how to modify certain design aspects and better address the question(s) of interest and/or adjust for incorrect assumptions. When planned carefully and applied in appropriate situations, a number of adaptive designs allow for scientifically sound conclusions: early stopping either for futility or for success, sample size reassessment, treatment selection, etc. Most of the current discussions regarding adaptive designs, focus however, on clinical trial applications in the (late) development phase of a novel drug. The aim of this review is to broaden this perspective and to demonstrate that adaptivity is a fundamentally important concept that can be applied to many different stages of drug discovery and development. We review the major statistical methods available for planning and analyzing adaptive designs and then move through the drug discovery and development process and identify possible opportunities for adaptivity. To illustrate the ideas, we refer to examples and case studies from the literature, where available. A brief discussion about regulatory perspectives, operational aspects, and some potential hurdles is also given. Drug Dev Res 70 : 169-190, 2009. r

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Maximum Tolerated Dose of Nalmefene in Patients Receiving Epidural Fentanyl and Dilute Bupivacaine for Postoperative Analgesia

Cited by 24 publications

References 6 publications

Comparison of the discriminative and neuroendocrine effects of centrally penetrating κ-opioid agonists in rhesus monkeys

Comparison of the discriminative and neuroendocrine effects of centrally penetrating κ-opioid agonists in rhesus monkeys

Sequential allocation trial design in anesthesia: an introduction to methods, modeling, and clinical applications

Adaptivity in drug discovery and development

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