Gabapentin Bioequivalence Study: Quantification By Liquid Chromatography Coupled To Mass Spectrometry

The study was performed to compare the bioavailability of two gabapentin 400 mg capsule formulation (Gabapentin from Arrow Farmacêutica S/A as test formulation and Neurontin ® from Pfizer, Brazil, as reference formulation) in 26 volunteers of both sexes. The study was conducted open with randomized two period crossover design and a one week wash out period. Plasma samples were obtained over a 48 hour interval. The gabapentin was analyzed by LC/MS/MS, in the presence of pracetamole as internal standard. With plasma concentration vs. time curves, data obtained from this metabolite, the following pharmacokinetics parameters were obtained: AUC 0-t, AUC 0-inf and C max. Geometric mean of gabapentin/Neurontin ® 400 mg individual percent ratio was 100.58% AUC 0-t, 101.35% for AUC 0-inf and 97.76% for C max. The 90% confidence intervals were 92.00 - 109.95%, 93.00 - 110.44%, 88.41 - 108.10%, respectively. Since the 90% confidence intervals for C max, AUC 0-t and AUC 0 -inf were within the 80 - 125% interval proposed by Food and Drug Administration, it was concluded that gabapentin 400 mg capsule was bioequivalent to Neurontin ® 400 mg capsule according to both the rate and extent of absorption. © 2011 Junior EA, et al.38187190Wattananat, T., Akarawut, W., Validated LC-MS-MS Method for the Determination of Gabapentin in Human Plasma: Application to a Bioequivalence Study (2009) J Chromatogr Sci, 47, pp. 868-871Stewart, B.H., Kagler, A.R., Thompson, P.R., Bockbrader, H.N., A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma (1993) Pharma Res, 10, pp. 276-281McLean, M.J., Gabapentin in the management of convulsive disorders (1999) Epilepsia, 40, pp. 39-50Goa, K.L., Sorkin, E.M., Gabapentin: A review of its pharmacological properties and clinical potential in epilepsy (1993) Drugs, 46, pp. 409-427Zhu, Z., Neirinck, L., High-performance liquid chromatographic method for the determination of gabapentin in human plasma (2002) J Chromatogr B Analyt Technol Biomed Life Sci, 779, pp. 307-312Sagirli, O., Cetin, S.M., Determination of gabapentin in human plasma and urine by high-performance liquid chromatography with UV-vis detection (2006) J Pharm Biomed Anal, 42, pp. 618-624Jalalizadeh, H., Souri, E., Tehrani, M.B., Jahangiri, A., Validated HPLC method for the determination of gabapentin in human plasma using precolumn derivatization with 1-fluoro-2,4-dinitrobenzene and its application to a pharmacokinetic study (2007) J Chromatogr B Analyt Technol Biomed Life Sci, 854, pp. 43-47Forrest, G., Sills, G.J., Leach, J.P., Brodie, M.J., Determination of gabapentin in plasma by high-performance liquid chromatography (1996) J Chromatogr B Analyt Technol Biomed Life Sci, 681, pp. 421-425Tang, P.H., Miles, M.V., Glauser, T.A., Degrauw, T., Automated microanalysis of gabapentin in human serum by high-performance liquid chromatography with fluorometric detection (1999) J Chromatogr B Analyt Technol Biomed Life Sci, 727, pp. 125-129Hassan, E.M., Belal, F., Al-Deeb, O.A., Khalil, N.Y., Spectrofluorimetric determination of vigabatrin and gabapentin in dosage forms and spiked plasma samples through derivatization with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (2001) J. 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A Mobility Determination Method for Parallel Platforms Based on the Lie Algebra of SE(3) and Its Subspaces

This contribution presents a screw theory-based method for determining the mobility of fully parallel platforms. The method is based on the application of three stages. The first stage involves the application of the intersection of subalgebras of Lie algebra, se(3), of the special Euclidean group, SE(3), associated with the legs of the platform. The second stage analyzes the possibility of the legs of the platform generating a sum or direct sum of two subalgebras of the Lie algebra, se(3). The last stage, if necessary, considers the possibility of the kinematic pairs of the legs satisfying certain velocity conditions; these conditions reduce the platform’s mobility analysis to one that can be solved using one of the two previous stages. Several examples are illustrated

Search for excited quarks in the y+jet final state in proton-proton collisions at s=8 TeV

A search for excited quarks decaying into the γ+jet final state is presented. The analysis is based on data corresponding to an integrated luminosity of 19.7 fb −1 collected by the CMS experiment in proton–proton collisions at s=8 TeV at the LHC. Events with photons and jets with high transverse momenta are selected and the γ+jet invariant mass distribution is studied to search for a resonance peak. The 95% confidence level upper limits on the product of cross section and branching fraction are evaluated as a function of the excited quark mass. Limits on excited quarks are presented as a function of their mass and coupling strength; masses below 3.5 TeV are excluded at 95% confidence level for unit couplings to their standard model partners

A synthesis method for 1-DOF mechanisms with a cusp in the configuration space

Significant progress has been made in the study of singularities of mechanisms. This research has, however, exclusively focused on situations where different motion branches intersect, i.e. bifurcation points of the configuration space (c-space). Other types of singularities have not been studied due to lack of mechanisms examples. In particular, mechanisms exhibiting cusp singularities in their c-space are almost unknown, besides a planar linkage presented by Connelly and Servatius, which served as an example where the common definition of rigidity fails. In this paper, a method for the synthesis of spatial 1-degree-of-freedom (1-DOF) cusp mechanisms is presented. This method consists in synthesizing the mechanical generator of a spatial curve with specific characteristics and then appropriately connecting this module with its mirrored version. Several examples are presented including a kinematotropic linkage, which is characterized by a singularity that is a cusp (1 DOF motion) and a bifurcation of a curve and a surface (2-DOF motion). It is discussed that all available methods for the local analysis of singularities fail at cusp singularities. The presented synthesis method allows for constructing mechanisms that shall initiate the research into the study of cusp singularities

Verification of the higher order kinematic analyses equations

In this contribution the higher order analyses equations for a kinematic chain are deduced by successive derivation of the velocity analysis equation. In order to simplify the process, a generic expression formed by the Jacobian matrix times a general vector of appropriate dimension is defined. Deriving this expression and forming similar generic expressions, it is possible to obtain first, second and third derivatives of the original expression. From these derivatives, the second -acceleration-, third -jerk- and fourth -jounce- order analyses equations are easily obtained. These equations are compared with those previously obtained by Lerbet and Duffy and his coworkers, and they are found to be in complete agreement. Finally, these expressions are employed to determine the local mobility of three single-loop kinematic chains in singular positions in which most of the techniques for the mobility determination fail. The first example is a kinematotropic linkage. In the second example, the expressions are employed to prove that a seemingly movable linkage is, in reality, a structure; an important detail in this example is that the expressions for the fourth order analysis are required. Finally, a reconfigurable linkage is dealt with, in the third example

Tamoxifen Inhibits Induction of the Mitochondrial Permeability Transition by Ca2+and Inorganic Phosphate

Tamoxifen (TAM) is a synthetic, nonsteroidal antiestrogenic agent that is widely prescribed in the treatment of estrogen-dependent neoplasias, including breast cancer. The mechanism of action has yet to be defined, but likely is independent of estrogen receptor binding. In light of its high lipophilicity and peroxyl radical scavenging activities, we hypothesized that TAM might be an effective inhibitor of the mitochondrial permeability transition (MPT), which is widely implicated in the mechanisms of chemical-induced tissue injury and apoptosis. The MPT was inducedin vitroby incubating freshly isolated rat liver mitochondria in 1 mM Pi with increasing concentrations of calcium. Induction of the MPT was characterized by the calcium-dependent depolarization of mitochondrial membrane potential, release of matrix calcium, and large amplitude swelling. Membrane potential and calcium release were measured with ion-selective electrodes; mitochondrial swelling was monitored spectrophotometrically. Preincubation with either cyclosporine A or TAM prevented, in a dose-dependent manner, the calcium-induced MPT. TAM also inhibited the calcium-induced release of matrix glutathione. TAM caused a time-dependent reversal of both the calcium-induced membrane depolarization and calcium release, suggesting that the effect was on the permeability transition pore and not due to inhibition of the mitochondrial calcium uniport. The results suggest that TAM mimics cyclosporine A to inhibit induction of the MPT and that this activity is not related to the antioxidant properties of TAM.http://www.sciencedirect.com/science/article/B6WXH-45M32S9-15/1/28db6017a9424db5c4c815c3e3ba2e9