Biomedical subjects

X Meng

Publications and source records attributed to X Meng.

At least 19 recordsLinked to original sources

PubMed2006

A tumor-specific conditionally replicative adenovirus vector expressing TRAIL for gene therapy of hepatocellular carcinoma.

We constructed a novel hepatocellular carcinoma-specific conditionally replicative adenovirus (CRAd). This adenovirus, designated Ad.HS4.AFP.E1A/TRAIL, expresses E1A to mediate viral replication and TRAIL to enhance HCC-killing efficacy under the control of a modified AFP promoter. An insulator HS-4 was placed in front of the AFP promoter to enhance the fidelity of the heterologous promoter. This virus was shown to have specific cytolytic activity in AFP-expressing HCC cells in vitro. Furthermore, the replication efficiency of Ad.HS4.AFP.E1A/TRAIL correlated well with AFP expression of the host cells, showing a 100-fold and 1 000 000-fold decrease in the low-and non-AFP-expressing HCC cells, respectively, compared to the high AFP-expressing HCC cells. An increase in mRNA of TRAIL and the elevated Caspase-3 activity were also observed in Ad.HS4.AFP.E1A/TRAIL-infected HCC cells. These results indicated that TRAIL expression from the viral vector activated the Caspase-3 enzymatic capacity and the HCC cells were sensitive to TRAIL. In vivo, Ad.HS4.AFP.E1A/TRAIL effectively prevented the growth of low AFP-expressing BEL-7404 xenografts. These results indicate that Ad.HS4.AFP.E1A/TRAIL could provide a new strategy of gene therapy for HCC.

Adenoviridae↗

PubMed2006

The use of enzyme technology for improved energy utilization from full-fat oilseeds. Part I: canola seed.

The effect of carbohydrase enzyme supplementation on energy utilization from full-fat canola seed was investigated in a TMEn assay with adult roosters and in a nutrient digestibility and growth performance study with broiler chickens. In the TMEn assay, enzyme preparations C (cellulase, 340 U/g), XG (xylanase, 63,600 U/g and glucanase, 48,300 U/g), P (pectinase, 10,000 U/g), and MC (mannanase, 10,900 U/g and cellulase, 600 U/ g), alone and in combination (C + P, C + XG, C + MC, P + XG, P + MC, XG + MC, C + P + XG, C + P + MC, and C + P + XG + MC), were evaluated at an inclusion level of 0.1%. On average, hammer-milled canola seed with a TMEn content of 3,642 kcal/kg showed an increase (P < 0.05) to 4,783 kcal/kg following supplementation with the enzyme blends C + P + XG, C + P + MC, and C + P + XG + MC. A similar pattern of increase (P < 0.05) in fat (80.4 vs. 63.5%) and nonstarch polysaccharide (NSP; 20.4 vs. 4.4%) digestibilities was observed. Enzyme combination C + P + XG was further evaluated in a 2-wk (5- to 18-d) trial with broiler chickens fed isonitrogenous and isoenergetic corn and soybean meal-based diets containing canola seed (15%), the corresponding canola meal (8.85%) plus canola oil (6.15%) mixture, or canola seed (15%) supplemented with 3 different levels (0.002, 0.01, or 0.05%) of the enzyme. Poorer (P < 0.05) feed:gain (1.412 vs. 1.344), lower (P < 0.05) total tract DM (65.9 vs. 70.7%) and fat (69.6 vs. 88.0%) digestibilities, lower AMEn content (2,963 vs. 3,200 kcal/kg), and lower ileal fat (65.6 vs. 85.6%) and protein (75.6 vs. 81.2%) digestibilities were observed for the canola seed diet compared with the canola meal plus canola oil diet. Enzyme supplementation of the canola seed diet resulted in an improvement (P < 0.05) in feed:gain; total tract DM, fat, and NSP digestibilities; AMEn content; and ileal fat digestibility. Although the enzyme effect on ileal and total tract fat digestibilities was significant at both high and medium inclusion levels, other parameters showed the significant improvement only when the highest inclusion rate of enzyme was used. These data support the need for carbohydrase enzyme supplements in poultry diets containing full-fat canola seed.

Animal Nutritional Physiological Phenomena↗

PubMed2006

The use of enzyme technology for improved energy utilization from full-fat oilseeds. Part II: flaxseed.

An in vitro incubation study was carried out to determine whether various carbohydrase preparations contained appropriate activities to target nonstarch polysaccharides (NSP) of full-fat flaxseed. Enzyme preparations C (cellulase, 340 U/g), XG (xylanase, 63,600 U/g and glucanase, 48,300 U/g), P (pectinase, 10,000 U/g), and MC (mannanase, 10,900 U/g and cellulase, 600 U/ g), alone and in combination (C + P, C + XG, P + XG, C + P + XG, C + P + MC, and C + P + XG + MC), were evaluated. Triplicate samples of defatted flaxseed meal (0.1 g) were incubated with 1% single enzymes or combinations at 45 degrees C and pH 5.2. A more pronounced degradation of NSP was achieved when the enzyme preparations were used in concert. Compared with the control (no enzyme) treatment, the degree of NSP degradation averaged 34.7% when the sample was incubated with the 3 most effective enzyme combinations (C + P + XG, C + P + MC, and C + P + XG + MC). The effect of carbohydrase enzyme supplementation on energy utilization from full-fat flaxseed was investigated in a TMEn assay with adult roosters. When compared with the nonsupplemented sample, an increase (P < 0.05) in TMEn content from 2,717 to 3,751 kcal/kg (on average) was observed for the flaxseed supplemented with enzymes C + P + XG, C + P + MC, and C + P + XG + MC. A similar pattern of increase (P < 0.05) in fat and NSP digestibilities was noted. Enzyme combination C + P + XG was further evaluated in a 2-wk (5- to 18-d) trial with broiler chickens fed a corn and soybean meal-based flaxseed (15%) diet or the flaxseed diet supplemented with the enzyme at 3 different levels: 0.002, 0.01, and 0.05%. When supplemented at the highest level, the enzyme blend improved (P < 0.05) feed:gain, total tract DM, fat and NSP digestibilities, AMEn content, and ileal fat digestibility. No effect of enzyme supplementation, regardless of the level used, on ileal protein digestibility and digesta viscosity was observed. The results of the current study suggest that multiactivity carbohydrase enzyme supplements may be used as a means to improve energy utilization from full-fat flaxseed and, thus, enhance its feeding value for poultry.

Animal Feed↗

PubMed2005

Cardio-ankle vascular index (CAVI) for the monitoring of the atherosclerosis after heart transplantation.

Atherosclerosis has been reported to progress rapidly after heart transplantation. A quantitative diagnosis is required for the diagnosis of atherosclerosis after heart transplantation. In this study, we compared brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) for the diagnosis. The average values of both baPWV and CAVI in the seven cases after heart transplantation were found to be signif-icantly large in comparison to the average values of the normal healthy people of the same age group. When comparisons were made before and after the heart transplantation in a particular case, CAVI was stable and baPWV changed sharply. A lot of parameters such as blood pressure, blood volume, etc. have been reported to influence baPWV. The results of this study suggested that CAVI was a stable parameter in comparison to baPWV even after heart transplantation. Thus, CAVI may be useful in the diagnosis of arteriosclerosis after heart transplantation.

Adolescent↗

PubMed2005

Degradation of cell wall polysaccharides by combinations of carbohydrase enzymes and their effect on nutrient utilization and broiler chicken performance.

In vitro incubation studies were carried out to determine if various carbohydrase preparations contained appropriate activities to target nonstarch polysaccharides (NSP) of wheat, soybean meal (SBM), canola meal, and peas. Triplicate samples (0.1 g) were incubated with a number of carbohydrase preparations (i.e., cellulase, pectinase, xylanase, glucanase, galactanase, and mannanase) or their combinations at 45 degrees C and pH 5.2. A more pronounced degradation of NSP was achieved when the enzyme preparations were used in concert. When compared with the control (nonenzyme treatment), the highest degree of NSP degradation reached was 37% for wheat, and 36, 26, and 28% for canola meal, SBM, and peas, respectively. Four enzyme combinations were studied further in a 2-wk (5 to 18 d of age) growth performance and nutrient digestibility trial with broiler chickens. All enzyme combinations were effective in improving (P < 0.05) weight gain, feed-to-gain ratio, AMEn, apparent ileal digestibilities of starch and protein, and apparent total tract digestibility of NSP in birds fed a wheat, wheat screening, SBM, canola meal, and peas-based diet. The most complex enzyme combination was found to be superior (P < 0.05) to others in improving ileal protein digestibility and feed-to-gain ratio. The effectiveness of this combination in elimination of the nutrient-encapsulating effect of cell walls was further evaluated in a balance study with adult roosters fed a conventionally ground full-fat canola seed. Enzyme addition increased (P < 0.05) NSP digestibility from 11.1 to 30.1%, which, in turn, resulted in a marked increase (P < 0.05) in TMEn value (4.176 vs 4.744 Mcal/kg) of the seed. It is evident from the present studies that the addition of an appropriate combination of carbohydrase enzymes to target cell wall polysaccharide structures could further improve enzyme efficacy in practical wheat, SBM, canola meal, and peas-based broiler diets.

Animal Nutritional Physiological Phenomena↗

PubMed2005

Nutritive values of corn, soybean meal, canola meal, and peas for broiler chickens as affected by a multicarbohydrase preparation of cell wall degrading enzymes.

The effect of a new multicarbohydrase supplement of cell wall degrading activities on the nutritive value of corn, soybean meal (SBM), canola meal (CM), and peas for broiler chickens was investigated. Four isoenergetic and isonitrogenous corn (69% corn), SBM (30% SBM, 59% corn), CM (30% CM, 54% corn), and pea (30% peas, 52% corn) diets, without or with enzyme supplementation, were formulated to meet NRC specifications for broiler chickens (except for AME and CP, which were at 95 and 92% of NRC requirements, respectively). The enzyme supplement supplied 1,000 U of xylanase, 400 U of glucanase, 1,000 U of pectinase, 120 U of cellulase, 280 U of mannanase, and 180 U of galactanase per kilogram of diet. Each diet was fed in a mash form to 9 replicate pens of 5 broilers from 5 to 18 d. When compared with the control treatment, enzyme addition to the corn diet improved (P < 0.05) feed-to-gain ratio, whereas the performance of birds fed the other 3 diets was not affected. An increase (P < 0.05) in total tract nonstarch polysaccharides (NSP) digestibility, ileal starch digestibility, and AMEn was observed in birds fed the enzyme-supplemented corn diet. An improvement (P < 0.05) in total tract NSP digestibility, ileal protein digestibility, and AMEn content with enzyme supplementation was observed for the SBM diet. However, nutrient digestibilities and AMEn of CM and pea diets were not affected (P > 0.05) by enzyme addition even though the NSP digestibilities increased significantly (P < 0.05). A significant increase (P < 0.05) in water-soluble NSP and a decrease (P < 0.05) in water-insoluble NSP concentration of ileal digesta was noted for birds fed all 4 enzyme-supplemented diets. It would appear from this study that the nutrient utilization of corn-SBM diet by broilers could be enhanced by using an appropriate multicarbohydrase enzyme supplement. The nutrient encapsulating effect of cell wall polysaccharides in SBM, CM, and peas may not be the only factor responsible for incomplete nutrient utilization. The improvement in feed efficiency and starch availability in birds fed corn diet likely resulted from the cell wall degrading activity of the enzyme supplement.

Animal Feed↗

PubMed2005

B-domain deleted recombinant factor VIII preparations are bioequivalent to a monoclonal antibody purified plasma-derived factor VIII concentrate: a randomized, three-way crossover study.

BACKGROUND: Deletion of the B-domain of recombinant blood coagulation factor VIII (BDDrFVIII) increases the manufacturing yield of the product but does not impair in vitro or in vivo functionality. BDDrFVIII (ReFacto) has been developed with the additional benefit of being formulated without human albumin. OBJECTIVE: The primary objective of this three-way crossover-design study was to compare the pharmacokinetic (PK) parameters of two BDDrFVIII formulations (one reconstituted with 5 mL of sterile water, the other reconstituted with 4 mL sodium chloride 0.9% USP) with those of a plasma-derived, full-length FVIII preparation (Hemofil M) in patients with haemophilia A to determine bioequivalence. METHODS: A series of blood samples were collected over a period of 48 h after i.v. administration of each of the FVIII preparations. Plasma FVIII activity was determined using a validated chromogenic substrate assay. Plasma FVIII activity vs. time curves was characterized for a standard set of PK parameter estimates. Two parameter estimates, the maximum plasma concentration (Cmax) and the area under plasma concentration vs. time curves (AUCs), were used to evaluate bioequivalence. The two preparations were considered bioequivalent if the 90% confidence intervals for the ratio of geometric means for Cmax and AUCs fell within the bioequivalence window of 80% to 125%. RESULTS/CONCLUSION: Results show that each BDDrFVIII formulation is bioequivalent to Hemofil M and the two formulations of BDDrFVIII are bioequivalent to each other.

Adolescent↗

PubMed2004

Domain structures in rutile in ultrahigh-pressure metamorphic rocks from Dabie Mountains, China.

According to the HRTEM study, the UHP jadeite-quartzite mineral (Rutile, TiO(2)) in Anhui Province, Dabie Mountains, China, has ultrastructures such as 011 two-dimensional commensurable modulated structures or superstructures, [011] twin domain structures, dislocations and crystal deformations. The SAED patterns and HRTEM images indicate the existence of the deformations and stacking faults on the interface of [011] twin crystal of rutile and its two-dimensional commensurate modulated structures with repetition period 0.753 nm (3d(011)) has tetragonal symmetry, cell parameters a = 3a0 = 1.377 nm (a0 = 0.459 nm), c = c0 = 0.3 nm. The modulated structures of rutile were probably caused by the isomorphic replacement of Ti(4+) and position modulation or occupation modulation of oxygen atoms in different degree; the deformation structures reveal that during the process of crystallization and mineralization, this mineral may be affected by the geological environment (such as temperature, pressure and stress), metamorphism and deformation.

Journal Article↗

PubMed2004

The effect of fat type, carbohydrase, and lipase addition on growth performance and nutrient utilization of young broilers fed wheat-based diets.

A 2 x 2 x 2 factorial experiment was conducted to evaluate the effects of fat type (beef tallow [50 g/kg diet] or canola oil [50 g/kg of diet]), carbohydrase addition (none or carbohydrases [0.4 g/kg diet]), and lipase addition (none or lipase [0.2 g/kg of diet]) on growth performance and nutrient utilization of male broilers fed a wheat-based diet from 5 to 18 d. The carbohydrase supplement contained xylanase, glucanase, cellulase, and other enzyme activities. The experimental diets were formulated to be suboptimal in major nutrients and each was fed in a mash form to 10 replicate pens of 5 broilers per pen. Body weight gain was not affected by fat type but a poorer feed/gain ratio (P < 0.001) was noted for tallow-containing diets. Regardless of fat type, carbohydrase enzyme supplementation improved (P < 0.001) BW gain and feed/gain ratio. There was no effect of lipase addition on chicken performance and nutrient utilization. When compared with canola oil, tallow-containing diets had a lower (P < 0.001) apparent fat digestibility and consequently a lower dietary AMEn content. Carbohydrase enzyme addition improved (P < 0.001) fat, starch, nitrogen, and nonstarch polysaccharide (NSP) digestibilities in the small intestine, improved AMEn, and reduced (P < 0.001) jejunal digesta viscosity in both fat types. Carbohydrase supplementation increased water-soluble (P < 0.001) and decreased water-insoluble (P < 0.001) NSP concentrations in the small intestine. The interaction between fat type and carbohydrase addition was only significant for fat digestibilities, with greater improvements seen for diets containing tallow. Significant interactions between carbohydrase addition and intestinal segment were noted for fat, starch, nitrogen, and NSP digestibilities, with the enzyme effects being greater in the jejunum than the ileum. It is evident from the present study that an appropriate carbohydrase preparation could eliminate the negative effects of soluble NSP on animal fat utilization in a wheat-based broiler diet.

Animal Nutritional Physiological Phenomena↗

PubMed2002

Transplantation of germ cells from glial cell line-derived neurotrophic factor-overexpressing mice to host testes depleted of endogenous spermatogenesis by fractionated irradiation.

With a novel method of eliminating spermatogenesis in host animals, male germ cells isolated from mice with targeted overexpression of glial cell line-derived neurotrophic factor (GDNF) were transplanted to evaluate their ability to reproduce the phenotype previously found in the transgenic animals. Successful depletion of endogenous spermatogenesis was achieved using fractionated ionizing irradiation. A dose of 1.5 Gy followed by a dose of 12 Gy after 24 h reduced the percentage of tubule cross-sections displaying endogenous spermatogenesis to approximately 3% and 10% as evidenced by histologic evaluation of testes at 12 and 21 wk, respectively, after irradiation. At this dose, no apparent harmful side effects were noted in the animals. Upon transplantation, GDNF-overexpressing germ cells were found to be able to repopulate the irradiated testes and to form clusters of spermatogonia-like cells resembling those found in the overexpressing donor mice. The cluster cells in transplanted host testes expressed human GDNF, as had been shown previously for clusters in donor animals, and both were strongly positive for the tyrosine kinase receptor Ret. Thus, we devised an efficient method for depleting the seminiferous epithelium of host mice without appreciable adverse effects. In these host mice, GDNF-overexpressing cells reproduced the aberrant phenotype found in the donor transgenic mice.

Animals↗

PubMed2001

Transient disruption of spermatogenesis by deregulated expression of neurturin in testis.

Two related ligands, glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), are expressed by Sertoli cells, but their cognate ligand-binding co-receptors, GDNF family receptor alpha1 and alpha2, are displayed by different germ cells suggesting different targets for the ligands. GDNF regulates cell fate decision of undifferentiated spermatogonia 'Science 287 (2000) 1489'. The role of NRTN was now approached by targeted overexpression in mouse testis. Between 3 and 5 weeks of age, transient degeneration of spermatogenic cells was observed in approximately 20% of all five transgenic lines generated. Spermatids and pachytene spermatocytes underwent segmental degeneration, if the rete testis was undilated. When it was dilated, the spermatids and spermatocytes were more generally depleted. After 5 weeks of age, spermatogenic defects were no more observed and the NRTN overexpressing mice were fertile. The data suggest that NRTN might regulate survival and differentiation of spermatocytes and spermatids, but the low penetrance indicates that either the transgene expression has not been high enough or NRTN is not as essential as GDNF for spermatogenesis.

Animals↗

PubMed2001

Traffic injury or attempted infanticide?

Two sewing needles were found in a woman's cranial cavity by X-ray examination after she had sustained traffic injury. After investigation and analysis, it has been confirmed that the sewing needles were inserted by others when she was an infant, and not by the traffic injury.

Accidents, Traffic↗

PubMed2001

Redox transformations of arsenic and iron in water treatment sludge during aging and TCLP extraction.

Laboratory experiments and modeling studies were performed to investigate the redox transformations of arsenic and iron in water treatment sludge during aging, and to evaluate the impact of those transformations on the leachability of arsenic determined with the U.S. EPA toxicity characteristic leaching procedure (TCLP). When the backwash suspension samples collected from a California surface water treatment plant were aged in closed containers for a few weeks, soluble arsenic increased from less than 5 microg/L to as high as 700 microg/L and then decreased dramatically because of biotic reduction of arsenate [As(V)], ferric oxyhydroxide, and sulfate. The experimental results and the thermodynamic models showed that arsenic mobility can be divided into three redox zones: (a) an adsorption zone at pe > 0, which is characterized by strong adsorption of As(V) on ferric oxyhydroxide; (b) a mobilization (transition) zone at -4.0 < pe < 0, where arsenic is released because of reduction of ferric oxyhydroxide to ferrous iron and As(V) to arsenite [As(III)]; and (c) a reductive fixation zone at pe < -4.0, where arsenic is immobilized by pyrite and other reduced solid phases. The TCLP substantially underestimated the leachability of arsenic in the anoxic sludge collected from sludge ponds because of the oxidation of Fe(II) and As(III) by oxygen. The leaching test should be performed in zero-headspace vessels or under nitrogen to minimize the transformations of the redox-sensitive chemical species.

Arsenic↗

PubMed2001

Suppressor of fused negatively regulates beta-catenin signaling.

Suppressor of fused (Su(fu)) is a negative regulator of the Hedgehog signaling pathway that controls the nuclear-cytoplasmic distribution of Gli/Ci transcription factors through direct protein-protein interactions. We show here that Su(fu) is present in a complex with the oncogenic transcriptional activator beta-catenin and functions as a negative regulator of T-cell factor (Tcf)-dependent transcription. Overexpression of Su(fu) in SW480 (APC(mut)) colon cancer cells in which beta-catenin protein is stabilized leads to a reduction in nuclear beta-catenin levels and in Tcf-dependent transcription. This effect of Su(fu) overexpression can be blocked by treatment of these cells with leptomycin B, a specific inhibitor of CRM1-mediated nuclear export. Overexpression of Su(fu) suppresses growth of SW480 (APC(mut)) tumor cells in nude mice. These observations indicate that Su(fu) negatively regulates beta-catenin signaling and that CRM-1-mediated nuclear export plays a role in this regulation. Our results also suggest that Su(fu) acts as a tumor suppressor.

Active Transport, Cell Nucleus↗

PubMed2001

An exclusively nuclear RNA-binding protein affects asymmetric localization of ASH1 mRNA and Ash1p in yeast.

The localization of ASH1 mRNA to the distal tip of budding yeast cells is essential for the proper regulation of mating type switching in Saccharomyces cerevisiae. A localization element that is predominantly in the 3'-untranslated region (UTR) can direct this mRNA to the bud. Using this element in the three-hybrid in vivo RNA-binding assay, we identified a protein, Loc1p, that binds in vitro directly to the wild-type ASH1 3'-UTR RNA, but not to a mutant RNA incapable of localizing to the bud nor to several other mRNAs. LOC1 codes for a novel protein that recognizes double-stranded RNA structures and is required for efficient localization of ASH1 mRNA. Accordingly, Ash1p gets symmetrically distributed between daughter and mother cells in a loc1 strain. Surprisingly, Loc1p was found to be strictly nuclear, unlike other known RNA-binding proteins involved in mRNA localization which shuttle between the nucleus and the cytoplasm. We propose that efficient cytoplasmic ASH1 mRNA localization requires a previous interaction with specific nuclear factors.

3' Untranslated Regions↗

PubMed2001

Promotion of seminomatous tumors by targeted overexpression of glial cell line-derived neurotrophic factor in mouse testis.

We show with transgenic mice that targeted overexpression of glial cell line-derived neurotrophic factor (GDNF) in undifferentiated spermatogonia promotes malignant testicular tumors, which express germ-cell markers. The tumors are invasive and contain aneuploid cells, but no distant metastases have been found. By several histological, molecular, and histochemical characteristics, the GDNF-induced tumors mimic classic seminomas in men, representing a useful experimental model for testicular germ-cell tumors. The data also show that a deregulated stimulation of a normal proto-oncogene by its ligand can be an initiative event in carcinogenesis.

Aneuploidy↗

PubMed2001

Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases.

Sorting nexins (SNX) comprise a family of proteins with homology to several yeast proteins, including Vps5p and Mvp1p, that are required for the sorting of proteins to the yeast vacuole. Human SNX1, -2, and -4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long form of the leptin receptor, a glycoprotein 130-associated receptor. We now describe a novel member of this family, SNX6, which interacts with members of the transforming growth factor-beta family of receptor serine-threonine kinases. These receptors belong to two classes: type II receptors that bind ligand, and type I receptors that are subsequently recruited to transduce the signal. Of the type II receptors, SNX6 was found to interact strongly with ActRIIB and more moderately with wild type and kinase-defective mutants of TbetaRII. Of the type I receptors, SNX6 was found to interact only with inactivated TbetaRI. SNXs 1-4 also interacted with the transforming growth factor-beta receptor family, showing different receptor preferences. Conversely, SNX6 behaved similarly to the other SNX proteins in its interactions with receptor tyrosine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation in vivo of oligomeric complexes. These findings are the first evidence for the association of the SNX family of molecules with receptor serine-threonine kinases.

Amino Acid Sequence↗

PubMed2001

Bioavailability of amiodarone tablets administered with and without food in healthy subjects.

The tablet form of amiodarone is indicated for the treatment of recurrent ventricular fibrillation or hemodynamically unstable ventricular tachycardia. It is recommended that the tablet be taken with meals in cases of gastrointestinal intolerance. However, the effect of food on its bioavailability is unknown. The primary objective of this study was to determine the effect of food on the bioavailability of amiodarone. This was a 2-period crossover study conducted in 30 healthy male subjects. Subjects were randomly assigned to 1 of 2 sequences in which the following 2 treatments were administered: (1) a single-dose of amiodarone (three 200-mg Cordarone tablets) after an overnight fast, and (2) the same dose immediately after a standard high-fat breakfast. Plasma concentrations of amiodarone and desethylamiodarone (DEA) were measured for 6 weeks after each dose. Food enhanced the extent of absorption, resulting in a peak concentration (Cmax) and area under the curve (AUCT) 3.8 and 2.4 times the respective values under fasting conditions. Food also significantly increased the rate of absorption, reducing the time (tmax) to Cmax from 7.1 to 4.5 hours. The effect of food on DEA levels was significant but less pronounced. An in vitro dissolution study confirmed a marked difference between amiodarone release under simulated fed and fasting conditions. Thus, food significantly enhances both the rate and extent of absorption of amiodarone, which is attributed partially to the effect of food on drug release from its formulation. Therefore, it is recommended that amiodarone tablets be taken consistently with meals.

Adult↗