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Institution

Research Triangle Park

NonprofitDurham, North Carolina, United States
About: Research Triangle Park is a nonprofit organization based out in Durham, North Carolina, United States. It is known for research contribution in the topics: Population & Environmental exposure. The organization has 24961 authors who have published 35800 publications receiving 1684504 citations. The organization is also known as: RTP.


Papers
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Journal ArticleDOI
TL;DR: In this paper, a study of the diffusion coefficients, D2, the distribution coefficients, κ2, and the permeability coefficients, P, of NaCl in various hydrophilic polymers was made with the assumptions that the free volume of a polymer/diluent system is linearly proportional to the volume fraction of diluent (H).
Abstract: Based on an analysis by the free volume theory of diffusion, a study of the diffusion coefficients, D2, the distribution coefficients, κ2, and the permeability coefficients, P, of NaCl in various hydrophilic polymers was made with the assumptions that the free volume of a polymer/diluent system is linearly proportional to the volume fraction of diluent (H), and that NaCl permeates only through polymer/diluent systems in which the diluent of polymers is also a good solvent of the solute (NaCl). The values of D2 (over five orders of magnitude) were found to vary exponentially with changes in 1/H, as expected from the free volume theory of diffusion, in a wide range of H-values and converge to the value of the diffusion constant of NaCl in pure water. The values of κ2 defined by g NaCl per cm3 polymer/g NaCl per cm3 solution were found to be more characteristic to the type of polymers particularly at a lower range of H-values. At higher ranges of H-values, k2 is nearly equal to H, however, at lower H, k2 values deviate significantly from the value of H and its extent was found to be greatly dependent on the chemical nature of polymers, whereas the diffusion coefficient follows the normal pattern predicted by the free volume theory. The values of P which are given by the product of D2 and k2 also were found to vary exponentially with changes in 1/H at higher range of H, however, at lower range of H it deviates from the relationship due to the varying dependence of factor k2 on 1/H.

423 citations

Journal ArticleDOI
TL;DR: A good correlation was found between the fraction of dose absorbed and the effective permeability for ten drugs covering a wide range of absorption characteristics, and the model was able to explain the oral plasma concentration profiles of atenolol.

423 citations

Journal ArticleDOI
TL;DR: The operational model has supplanted analysis of drug-receptor interaction in functional systems whereas the extended ternary complex model is used routinely to simulate quantitatively G-protein-coupled receptor (GPCR) behavior.

423 citations

Journal ArticleDOI
TL;DR: To evaluate the efficacy and safety of lacosamide when added to 1 or 2 antiepileptic drugs (AEDs) in adults with uncontrolled partial‐onset seizures, and assess plasma concentrations of concomitant AEDs to determine any potential for drug interactions.
Abstract: Summary: Purpose: To evaluate the efficacy and safety of lacosamide when added to 1 or 2 antiepileptic drugs (AEDs) in adults with uncontrolled partial-onset seizures, and assess plasma concentrations of concomitant AEDs to determine any potential for drug interactions. Methods: During this multicenter, double-blind, placebocontrolled trial, patients were randomized to placebo or lacosamide 200, 400, or 600 mg/day after an 8-week baseline period. Lacosamide was titrated in weekly increments of 100 mg/day over 6 weeks and maintained for 12 weeks. Results were analyzed on an intention-to-treat basis. Results: Four hundred eighteen patients were randomized and received trial medication; 312 completed the trial. The median percent reduction in seizure frequency per 28 days was 10%, 26%, 39%, and 40% in the placebo, lacosamide 200, 400, and 600 mg/day treatment groups, respectively. The median percent reduction in seizure frequency over placebo was significant for lacosamide 400 mg/day (p = 0.0023) and 600 mg/day (p = 0.0084). The 50% responder rates were 22%, 33%, 41%, and 38% for placebo, lacosamide 200, 400, and 600 mg/day, respectively. The 50% responder rate over placebo was significant for lacosamide 400 mg/day (p = 0.0038) and 600 mg/day (p = 0.0141). Adverse events that appeared doserelated included dizziness, nausea, fatigue, ataxia, vision abnormal, diplopia, and nystagmus. Lacosamide did not affect mean plasma concentrations of concomitantly administered AEDs. Conclusions: In this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial-onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED. Key Words: Epilepsy— Partial-onset seizures—Lacosamide—Antiepileptic drugs— Randomized controlled trials. Lacosamide (SPM 927, formerly harkoseride), the R-enantiomer of 2-acetamido-N-benzyl-3-methoxypropionamide, is a new chemical entity being developed as an oral formulation (Bialer et al., 2004) for the treatment of epilepsy and neuropathic pain. In addition, an intravenous formulation is being developed for short-term replacement of oral lacosamide in patients with partial-onset seizures. Based on recent experimental studies, lacosamide appears to have a dual mode of action—enhancement of sodium-channel slow inactivation and modulation of collapsin response mediator protein-2 (CRMP-2) (Stoehr et al., 2006)—both of which are novel mechanisms for an antiepileptic drug (AED). Without affecting fast inactivation, lacosamide appears to selectively enhance sodium

423 citations

Journal ArticleDOI
TL;DR: An estimator is proposed for the parameter C = 4Nc where N is the population size and c is the recombination rate and the median and mode of the distribution of the estimator are close to the true value for all parameter values examined.
Abstract: An estimator is proposed for the parameter C = 4Nc. where N is the population size and c is the recombination rate. The estimator is appropriate for use with sequence or restriction site data from random samples from within populations. Properties of the estimator are investigated for an infinite-sites neutral model using Monte Carlo simulations. The median and mode of the distribution of the estimator are close to the true value for all parameter values examined, but large data sets are required to obtain reliable estimates.

422 citations


Authors

Showing all 25006 results

NameH-indexPapersCitations
Douglas G. Altman2531001680344
Lewis C. Cantley196748169037
Ronald Klein1941305149140
Daniel J. Jacob16265676530
Christopher P. Cannon1511118108906
James B. Meigs147574115899
Lawrence Corey14677378105
Jeremy K. Nicholson14177380275
Paul M. Matthews14061788802
Herbert Y. Meltzer137114881371
Charles J. Yeo13667276424
Benjamin F. Cravatt13166661932
Timothy R. Billiar13183866133
Peter Brown12990868853
King K. Holmes12460656192
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202317
202277
2021988
20201,001
20191,035
20181,051