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1.
C Pantarotto V Crunelli J Lanzoni A Frigerio A Quattrone 《Analytical biochemistry》1979,93(1):115-123
A specific and sensitive method is described for the simultaneous determination of carbamazepineand carbamazepine-10,11-epoxide in biological specimens by combined gas chromatography-mass spectrometry. Cytenamide is used as the internal standard for quantitation. Kinetics of the distribution of the drug and its metabolite in plasma and in different areas of rat brain are reported. Determinations are possible at the nanogram level. 相似文献
2.
A novel, sensitive and rapid CL method coupled with high‐performance liquid chromatography separation for the determination of carbamazepine is described. The method was based on the fact that carbamazepine could significantly enhance the chemiluminescence of the reaction of cerium sulfate and tris(2,2‐bipyridyl) ruthenium(II) in the presence of acid. The chromatographic separation was performed on a Kromasil® (Sigma‐Aldrich) TM RP‐C18 column (id: 150 mm × 4.6 mm, particle size: 5 µm, pore size: 100 Å) with a mobile phase consisting of methanol–water‐glacial acetic acid (70:29:1, v/v/v) at a flowrate of 1.0 mL/min, the total analysis time was within 650 s. Under optimal conditions, CL intensity was linear for carbamazepine in the range 2.0 × 10?8 ~ 4.0 × 10?5 g/mL, with a detection limit of 6.0 × 10?9 g/mL (S/N = 3) and the relative standard detection was 2.5% for 2.0 × 10?6 g/mL (n = 11). This method was successfully applied to the analysis of carbamazepine in human urine and serum samples. The possible mechanism of the CL reaction is also discussed briefly. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
3.
Danielsson C Azarbayjani F Sköld AC Sjögren N Danielsson BR 《Birth defects research. Part A, Clinical and molecular teratology》2007,79(8):595-603
BACKGROUND: The antiepileptic drugs (AEDs) phenytoin, phenobarbital, dimethadione, and carbamazepine cause a similar pattern of malformations in humans, with an increased risk after polytherapy. The teratogenicity has been linked to cardiac rhythm disturbances and hypoxic damage as a consequence of their common potential to inhibit a specific potassium ion current (IKr). The IKr is of major importance for embryonic cardiac repolarization and rhythm regulation. This study investigated whether these AEDs cause irregular rhythm and if various combinations of AEDs result in higher arrhythmia risk than exposure to a single AED. METHODS: The effects on heart rhythm of a single AED (monotherapy), and of various combinations (polytherapy) of AEDs, in gestational day 10 C57BL mouse embryos in culture were analyzed and graphically illustrated during a 25 s recording with a digitalization technique. RESULTS: All of the studied AEDs caused increased intervals between heartbeats (resulting in bradycardia) and large variations in the interval between heartbeats (resulting in irregular rhythm) in a concentration-dependent manner in cultured mouse embryos. Dimethadione caused irregular rhythm at concentrations within and phenytoin slightly above the therapeutic ranges. Polytherapy resulted in more substantial prolongation of the mean interval between heartbeats (>60 ms) than monotherapy at clinically relevant concentrations. CONCLUSIONS: The results suggest that polytherapy more than monotherapy causes substantial prolongation of the cardiac repolarization, a marker associated with high risk of developing irregular rhythm during longer exposure periods (days to months). This supports the idea that the increased risk for malformations following polytherapy is linked to an increased risk for cardiac rhythm disturbances. 相似文献
4.
Lieb K Treffurth Y Hamke M Akundi RS von Kleinsorgen M Fiebich BL 《Journal of neurochemistry》2003,86(1):69-76
The neuropeptide substance P (SP) has been hypothesized to be involved in the etiopathology of affective disorders. This hypothesis is based on the findings that neurokinin-1-receptor antagonists have antidepressant effects in depressed patients and that SP may worsen mood. In this study, we investigated the effect of the mood-stabilizing agents valproic acid (VPA), carbamazepine, and lithium on SP-induced gene expression. As a model system, we used primary rat astrocytes and human astrocytoma cells, which both express functional SP-receptors and, upon stimulation with SP, synthesize interleukin-6 (IL-6), a cytokine which has been shown to be elevated during the acute depressive state. We found that VPA dose-dependently inhibited SP-induced IL-6 synthesis which was seen with pre-incubation periods of 30 min, 3, 7 and 14 days, whereas carbamazepine and lithium showed no inhibitory effect. The inhibitory effect of VPA was not mediated by inhibition of the stress-regulated kinases p38 and p42/44 (Erk1/2) but by inhibition of protein kinase C epsilon activation. Furthermore, VPA down-regulated the expression of the substance P receptor (neurokinin(NK)-1-receptor) as assessed by real-time PCR. Whether both mechanisms contribute to the mood-stabilizing properties of VPA has to be evaluated in further studies. 相似文献
5.
The purpose of this research was to improve the stability of carbamazepine (CBZ) bulk powder under high humidity by surface
modification. The surface-modified anhydrates of CBZ were obtained in a specially designed surface modification apparatus
at 60°C via the adsorption of n-butanol, and powder x-ray diffraction, Fourier-Transformed Infrared spectra, and differential
scanning calorimetry were used to determine the crystalline characteristics of the samples. The hydration process of intact
and surface-modified CBZ anhydrate at 97% relative humidity (RH) and 40±1°C was automatically monitored by using isothermal
microcalorimetry (IMC). The dissolution test for surface-modified samples (20 mg) was performed in 900 mL of distilled water
at 37±0.5°C with stirring by a paddle at 100 rpm as in the Japanese Pharmacopoeia XIII. The heat flow profiles of hydration
of intact and surface-modified CBZ anhydrates at 97% RH by using IMC profiles showed a maximum peak at around 10 hours and
45 hours after 0 and 10 hours of induction, respectively. The result indicated that hydration of CBZ anhydrate was completely
inhibited at the initial stage by surface modification of n-butanol and thereafter transformed into dihydrate. The hydration
of surface-modified samples followed a 2-dimensional phase boundary process with an induction period (IP). The IP of intact and surface-modified samples decreased with increase of the reaction temperature, and the hydration rate
constant (k) increased with increase of the temperature. The crystal growth rate constants of nuclei of the intact sample were significantly
larger than the surface-modified samples at each temperature. The activation energy (E) of nuclei formation and crystal growth process for hydration of surface-modified CBZ anhydrate were evaluated to be 20.1
and 32.5 kJ/mol, respectively, from Arrhenius plots, but the Es of intact anhydrate were 56.3 and 26.8 kJ/mol, respectively. The dissolution profiles showed that the surface-modified sample
dissolved faster than the intact sample at the initial stage. The dissolution kinetics were analyzed based on the Hixon-Crowell
equation, and the dissolution rate constants for intact and surface-modified anhydrates were found to be 0.0102±0.008 mg1/3 min−1 and 0.1442±0.0482 mg1/3·min−1. The surface-modified anhydrate powders were more stable than the nonmodified samples under high humidity and showed resistance
against moisture. However, surface modification induced rapid dissolution in water compared to the control. 相似文献
6.
Effects of the antiepileptic drug carbamazepine on nerve action potential and transmitter release in mouse neuroblastoma-glioma hybrid cells (NG108-15) and the frog neuromuscular junction were studied. Carbamazepine within a concentration range of 0.1–0.5 mmol/L reduced the peak height of the action potential of the NG108-15 cells, whereas the membrane potential and membrane resistance were unaffected. Voltage clamp revealed that the decrease in the action potential was due to the blockage of the Na+, delayed K+ and transient Ca2+ currents. Carbamazepine did not affect Ca2+-activated and A type K+ currents and long-lasting Ca2+ current. In the frog neuromuscular junction, carbamazepine decreased the mean quantal content by a parallel shift in the frequency augmentation–potentiation (FAP) relation. It is concluded that carbamazepine blocks the voltage-dependent Na+, delayed K+, and transient Ca2+ currents and quantal transmitter release through a decrease of nerve excitation. 相似文献
7.
Terence A. Ketter Mark A. Frye Gabriela Corá-Locatelli Timothy A. Kimbrell Robert M. Post 《Cellular and molecular neurobiology》1999,19(4):511-532
1. The mood stabilizers lithium, carbamazepine (CBZ), and valproate (VPA), have differing pharmacokinetics, structures, mechanisms of action, efficacy spectra, and adverse effects. Lithium has a low therapeutic index and is renally excreted and hence has renally-mediated but not hepatically-mediated drug–drug interactions.2. CBZ has multiple problematic drug–drug interactions due to its low therapeutic index, metabolism primarily by a single isoform (CYP3A3/4), active epoxide metabolite, susceptibility to CYP3A3/4 or epoxide hydrolase inhibitors, and ability to induce drug metabolism (via both cytochrome P450 oxidation and conjugation). In contrast, VPA has less prominent neurotoxicity and three principal metabolic pathways, rendering it less susceptible to toxicity due to inhibition of its metabolism. However, VPA can increase plasma concentrations of some drugs by inhibiting metabolism and increase free fractions of certain medications by displacing them from plasma proteins.3. Older anticonvulsants such as phenobarbital and phenytoin induce hepatic metabolism, may produce toxicity due to inhibition of their metabolism, and have not gained general acceptance in the treatment of primary psychiatric disorders.4. The newer anticonvulsants felbamate, lamotrigine, topiramate, and tiagabine have different hepatically-mediated drug–drug interactions, while the renally excreted gabapentin lacks hepatic drug–drug interactions but may have reduced bioavailability at higher doses.5. Investigational anticonvulsants such as oxcarbazepine, vigabatrin, and zonisamide appear to have improved pharmacokinetic profiles compared to older agents.6. Thus, several of the newer anticonvulsants lack the problematic drug-drug interactions seen with older agents, and some may even (based on their mechanisms of action and preliminary preclinical and clinical data) ultimately prove to have novel psychotropic effects. 相似文献
8.
The objective of this work was to study dissolution enhancement efficiency and solid dispersion formation ability of hydrophilic
swellable polymers such as sodium carboxymethyl cellulose (Na-CMC), sodium starch glycolate (SSG), pregelatinized starch (PGS),
and hydroxypropylmethyl cellulose (HPMC) with carbamazepine using 32 full factorial design for each of the polymers. Solid dispersions of carbamazepine were prepared using solvent evaporation
method with around 70% solvent recovery. The independent variables were the amount of polymer and organic solvent. The dependent
variables assessed were percentage drug dissolved at various time points and dispersion efficiency (ie, in terms of particle
size of solid dispersion). Solid dispersions were evaluated for percentage drug dissolved, wettability, differential scanning
calorimetry, scanning electron microscopy, and angle of repose. Multiple linear regression of results obtained led to equations,
which generated contour plots to relate the dependent variables. Similarity factor and mean dissolution time were used to
compare dissolution patterns obtained in distilled water and simulated gastric fluid United States Pharmacopeia (USP) XXVI
of pH 1.2. Maximum drug dissolution was obtained with polymer order Na-CMC>SSG>PGS>HPMC. Particle size of drug was reduced
≈ 10–15, 3–5, 5–7, and 10–25 times in Na-CMC, SSG, PGS, and HPMC solid dispersions, respectively; whereas wettability of solid
dispersions was found in the order of Na-CMC>HPMC>PGS>SSG. Angle of repose was found to be in the range of 29° to 35° for
all solid dispersions, which shows good flowability characteristics. HPMC showed increase in drug dissolution up to an optimized
level; however, furthers increase in its concentration decreased drug dissolution.
Published: April 6, 2007 相似文献
9.
Summary and Conclusion An attempt was made to develop a gastroretentive drug delivery system of carbamazepine using HPMC, sodium bicarbonate, and
EC as matrixing agent, gas-generating agent, and floating enhancer, respectively. A simplex lattice design was applied to
investigate the combined effect of 3 formulation variables (ie, amount of HPMC (X
1), EC (X
2), and sodium bicarbonate (X
3). Results of multiple regression analysis indicated that low levels ofX
1 andX
2 and a high level ofX
3 should be used to manufacture the tablet formulation with desired in vitro floating time and dissolution. Formulation S3
was selected as a promising formulation and was found stable at 40°C temperature and 75% RH for 3 months.
Published: February 9, 2007 相似文献
10.
The goal of this research was a phenomenological study of the effect of environmental factors on the dehydration behavior
of carbamazepine dihydrate. Dehydration experiments were performed in an automated vapor sorption apparatus under a variety
of conditions, and weight loss was monitored as a function of time. In addition to lattice water, carbamazepine dihydrate
contained a significant amount of physically bound water. Based on the kinetics of water loss, it was possible to differentiate
between the removal of physically bound water and the lattice water. The activation energy for the 2 processes was 44 and
88 kJ/mol, respectively. As expected, the dehydration rate of carbamazepine dihydrate decreased with an increase in water
vapor pressure. While dehydration at 0% relative humidity (RH) resulted in an amorphous anhydrate, the crystallinity of the
anhydrate increased as a function of the RH of dehydration. A method was developed for in situ crystallinity determination
of the anhydrate formed. Dehydration in the presence of the ethanol vapor was a 2-step process, and the fraction dehydrated
at each step was a function of the ethanol vapor pressure. We hypothesize the formation of an intermediate lower hydrate phase
with unknown water stoichiometry. An increase in the ethanol vapor pressure first led to a decrease in the dehydration rate
followed by an increase. In summary, the dehydration behavior of carbamazepine dihydrate was evaluated at different vapor
pressures of water and ethanol. Using the water sorption apparatus, it was possible to (1) differentiate between the removal
of physically bound and lattice water, and (2) develop a method for quantifying, in situ, the crystallinity of the product
(anhydrate) phase. 相似文献