Reproducibility of peripapillary, optic nerve head and macular vessel density by OCT-A according to glaucoma severity staging.

OBJECTIVE: To assess the reproducibility of peripapillary, optic nerve head (PP-ONH) and macular vessel density (VD) by Spectral Domain optical coherence tomography angiography (SD OCT-A) in glaucoma patients and healthy subjects. METHODS: Cross-sectional study assessing 63 eyes of 63 subjects, including 33 glaucoma patients and 30 healthy subjects. Glaucoma was classified in mild, moderate, or advanced. Two consecutive scans were acquired by Spectralis Module OCT-A (Heidelberg, Germany), and provided images of the superficial vascular complex (SVC), nerve fiber layer vascular plexus (NFLVP), superficial vascular plexus (SVP); deep vascular complex (DVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP). VD (%) was calculated by AngioTool. Intraclass correlation coefficients (ICCs) and coefficients of variation (CV) were calculated. RESULTS: Among PP-ONH VD, better ICC presented advanced (ICC 0.86-0.96) and moderate glaucoma (ICC 0.83-0.97) compared with mild glaucoma (0.64-0.86). For the macular VD reproducibility, ICC results for superficial retinal layers were better for mild glaucoma (0.94-0.96) followed by moderated (0.88-0.93) and advanced glaucoma (0.85-0.91), and for deeper retinal layers ICC was better for moderate glaucoma (0.95-0.96) followed by advanced (0.80-0.86) and mild glaucoma (0.74-0.91). CVs ranged from 2.2% to 10.94%. Among healthy subjects, ICCs for the PP-ONH VD measurements (0.91-0.99) and for the macular VD measurements (0.93-0.97) were excellent in all layers, with CVs from 1.65% to 10.33%. CONCLUSIONS: SD OCT-A used to quantify macular and PP-ONH VD showed excellent and good reproducibility in most layers of the retina, both in healthy subjects and in glaucoma patients regardless of the severity of the disease.

Peripapillary and optic nerve head vessel density of glaucoma and healthy subjects from Afro-Caribbean and European descent: A pilot study.

PURPOSE: To compare the peripapillary and optic nerve head vessel density (PP-ONH VD) between glaucoma patients (all, early, moderated, and advanced) and healthy subjects of Afro-Caribbean descent (AD) and European descent (ED). METHODS: This was a cross-sectional study. One eye was evaluated in 90 subjects, including 66 glaucoma patients and 24 healthy subjects, who underwent PP-ONH VD imaging using SPECTRALIS® Optical Coherence Tomography Angiography (OCT-A). We analysed the superficial vascular complex using the AngioTool version 0.6a software. The correlation between the PP-ONH VD and visual field mean deviation (MD) was evaluated using a scatter plot and Spearman's rho correlation coefficient. RESULTS: Among the healthy subjects, the AD group had a lower superficial PP-ONH VD [43.29±3.25% (mean±standard deviation)] than the ED group (46.06±1.75%) (P=0.016). Overall, superficial PP-ONH VD did not show any significant differences between the total AD and ED glaucoma patients or in the subgroup analyses (early/moderate/advanced) (AD: 32.73±6.70%, 37.11±5.72%, 32.48±5.73%, 27.76±4.74%, respectively; ED: 33.94±6.89%, 38.52±3.82%, 35.56±4.18%; 27.65±6.31%, respectively) (P>0.05 for all). A strong, statistically significant correlation was established between vessel density and mean deviation among AD and ED glaucoma patients (r=0.709 and r=0.704, respectively) (P<0.001 for both). CONCLUSION: This pilot study shows that healthy subjects of AD had lower peripapillary and optic nerve head superficial vessel density than healthy subjects of ED, but no significant differences were found between AD and ED glaucoma groups (all, early, moderate, or advanced).

Relative bioavailability study with two oral formulations of topiramate using a validated UPLC-MS/MS method.

Changes in bioavailability of anticonvulsant drugs such as topiramate may cause loss of or worsened seizure control. Thus, the purpose of this study was to evaluate, in a double-blind crossover design, the bioavailability between two oral formulations of topiramate in healthy volunteers after a single dose. The protocol, approved by the Institutional Committee of Ethics, consisted of administration of 1 tablet of 100 mg of topiramate of each formulation (Toprel and Topamax), to 20 healthy volunteers after a 12 h overnight fast, using an open, two-period, randomized, crossover and double-blind design. Thus, the plasma concentrations (Cp) of topiramate were measured at predetermined intervals of time, from 0 to 24 h, using a validated UPLC-MS/MS method. Based on plasma concentration-time profiles we obtained the following pharmacokinetic parameters: AUC(0-inf) 63,418.31 +/- 22,141.69 and 67,094.70 +/- 22,487.2 ngh/ml; AUC0-24: 30,421.02 +/- 9,964.0 and 30,489.35 +/- 9,407.17, ng x h/ml; tmax: 2.77 +/- 1.76 and 1.95 +/- 1.89 h; C(max): 2,143.33 +/- 724.26 and 2,262.51 +/- 751.12 ng/ml, for A (Toprel) and B (Topamax), respectively. All these differences were not statically significant with 90% confidence interval. The test of bioequivalence showed that Cmax, AUC(0-24) and AUC(0-inf) parameters are found within the range of 0.8 - 1.25 recommended by the FDA with a probability of bioequivalence of 100%. In accordance with these results, we can conclude that Toprel 100 mg, A (Test), is a bioequivalent generic and interchangeable with Topamax 100 mg, B (Reference).

Association analysis in a Latin American population revealed ethnic differences in rheumatoid arthritis-associated SNPs in Caucasian and Asian populations.

Large genome-wide association studies (GWAS) have increased our knowledge of the genetic risk factors of rheumatoid arthritis (RA). However, little is known about genetic susceptibility in populations with a large admixture of Amerindian ancestry. The aim of the present study was to test the generalizability of previously reported RA loci in a Latin American (LA) population with admixed ancestry. We selected 128 single nucleotide polymorphisms (SNPs) in linkage equilibrium, with high association to RA in multiple populations of non-Amerindian origin. Genotyping of 118 SNPs was performed in 313 RA patients/487 healthy control subjects by mid-density arrays of polymerase chain reaction (PCR). Some of the identified associations were validated in an additional cohort (250 cases/290 controls). One marker, the SNP rs2451258, located upstream of T Cell Activation RhoGTPase Activating Protein (TAGAP) gene, showed significant association with RA (p = 5 × 10-3), whereas 18 markers exhibited suggestive associations (p < 0.05). Haplotype testing showed association of some groups of adjacent SNPs around the signal transducer and activator of transcription 4 (STAT4) gene (p = 9.82 × 10-3 to 2.04 × 10-3) with RA. Our major finding was little replication of previously reported genetic associations with RA. These results suggest that performing GWAS and admixture mapping in LA populations has the potential to reveal novel loci associated with RA. This in turn might help to gain insight into the 'pathogenomics' of this disease and to explore trans-population differences for RA in general.

Management of corneal neurotrophic ulcers with Cacicol®-RGTA (ReGeneraTing Agent): a case series. / Manejo de las úlceras corneales neurotróficas con Cacicol®- ReGeneraTing Agent: serie de casos.

PURPOSE: Neurotrophic corneal ulcers are difficult to treat, and the conventional treatment often results in failure. A new matrix regenerating agent ("ReGeneraTing Agents"), Cacicol® (Laboratoires Théa), has demonstrated good results over the last few years. Therefore, the aim of this study was to evaluate the response to Cacicol® in a series of cases with neurotrophic corneal ulcers. METHODS: Retrospective case series looking at 11 patients with corneal ulcers unresponsive to conventional therapy that underwent treatment with Cacicol®. One cycle included 1 drop every two days for 5 days. RESULTS: The range of conventional therapy prior to Cacicol® was 0-91 days. On introducing Cacicol® 82% (9/11) of the cases were cured, and 18% (2/11) failed, requiring an amniotic membrane transplant or penetrating keratoplasty. The healing only required one cycle of Cacicol® in 67% (6/9) of the patients. More than one cycle of Cacicol® was needed in 45% (5/11) patients. One corneal bacterial ulcer responded favourably and one case related to Acanthamoeba did not respond. Most of the patients improved or maintained their visual acuity. CONCLUSION: Cacicol® was a useful therapy in a high number of difficult neurotrophic corneal ulcers, including corneal infections. Some cases may require more than one cycle of Cacicol® or used as first-line treatment in order to achieve the desired result.

Vitreous haemorrhage a rare manifestation of retinal astrocytic hamartoma: a paediatric case report. / Hemorragia vítrea una rara manifestación del hamartoma astrocítico retiniano: a propósito de un caso pediátrico.

INTRODUCTION: Retinal astrocytic hamartoma is generally an asymptomatic benign tumour that may or may not be associated with the tuberous sclerosis complex. Haemorrhage is a rare presentation. CASE REPORT: The case concerns a 12-year-old patient with "a black spot" vision in the upper temporal hemifield of the right eye, who referred a similar episode 2 years ago. The anterior pole was normal in the slit lamp. A mass of translucent white-yellow peri-papillary appearance and vitreous peri-papillary haemorrhage was observed in funduscopy. The autofluorescence, fluorescence angiography, and optical coherence tomography characteristics were all compatible with retinal astrocytic hamartoma. Complementary studies (serology and X-rays) and the complete clinical examination rule out associated systemic involvement. The patient was followed-up closely until the vitreous haemorrhage was reabsorbed. CONCLUSION: Vitreous haemorrhage is a rare complication of Retinal astrocytic hamartoma and funduscopic exploration is difficult. Systemic involvement should be ruled out.

High prevalence of clarithromycin resistance and effect on Helicobacter pylori eradication in a population from Santiago, Chile: cohort study and meta-analysis.

Helicobacter pylori (H. pylori) eradication using standard triple therapy (STT) with proton pump inhibitors (PPI), amoxicillin and clarithromycin (CLA) has been the standard in Latin America. However, CLA resistance is a rising problem affecting eradication rates. Genetic polymorphisms of CYP2C19, a PPI metabolizer may also affect eradication. The primary aims of this study were to evaluate the effect of clarithromycin resistance on H. pylori eradication in a population from Santiago, and to establish the pooled clarithromycin resistance in Santiago, Chile. Symptomatic adult patients attending a tertiary hospital in Santiago were recruited for this study. CLA resistance and the polymorphisms of CYP2C19 were determined on DNA extracted from gastric biopsies, using PCR. The STT was indicated for 14 days and eradication was determined by a urea breath test 4-6 weeks after therapy. A meta-analysis of CLA resistance studies among adult residents in Santiago was performed. Seventy-three out of 121 consecutive patients had positive rapid urease test (RUT) and received STT. Sixty-nine patients (95%) completed the study. The H. pylori eradication rate was 63% and the prevalence of CLA resistance was 26%. According to the CYP2C19 polymorphisms, 79.5% of the RUT-positive patients were extensive metabolizers. Multivariable analyses showed that only CLA resistance was significantly and inversely associated with failure of eradication (OR: 0.13; 95% confidence interval [95% CI], 0.04-0.49). A meta-analysis of two previous studies and our sample set (combined n = 194) yielded to a pooled prevalence of CLA resistance of 31.3% (95% CI 23.9-38.7). Our study shows that CLA resistance is associated with failure of H. pylori eradication. Given the high pooled prevalence of CLA resistance, consideration of CLA free therapies in Santiago is warranted. We could recommend bismuth quadruple therapy or high-dose dual therapy, according to bismuth availability. Further studies need to evaluate the best therapy.

Neonatal vitamin D status at birth at latitude 32 degrees 72': evidence of deficiency.

OBJECTIVE: With vitamin D deficiency as a serious public health problem, vitamin D status at birth was measured in neonates at latitude 32 degrees 72' (southeastern United States). STUDY DESIGN: In umbilical cord blood, vitamin D status, demonstrated by circulating 25-hydroxyvitamin D, was measured and related to race and season of birth. RESULT: The mean+/-standard deviation of 25-hydroxyvitamin D in 100 cord blood samples was 13.5+/-8.3 ng/ml for the cohort. African-American infants, with a mean+/-standard deviation of 10.5+/-6.0 ng/ml, demonstrated significantly lower vitamin D status than Caucasian infants, with a mean+/-standard deviation of 19.5+/-9.6 ng/ml (P<0.0001). By season, the mean 25-hydroxyvitamin D level at birth in November-March compared to April-October was 11.3 ng/ml lower in Caucasian infants (from 29.0 to 17.7 ng/ml) and 3 ng/ml lower in African-American infants (from 13.1 to 10.1 ng/ml). CONCLUSION: The prevalence of vitamin D insufficiency is high in this cohort. African-American infants demonstrate significantly lower vitamin D status at birth than Caucasian infants. Seasonality, while significant in both groups, had a greater impact on the vitamin D status of Caucasian newborns.

[Tesio catheters for long-term hemodialysis: our experience in a comarcal hospital]. / Catêteres de Tesio permanentes para realización de hemodiálisis crónica: nuestra experiencia en un hospital comarcal.

INTRODUCTION: Good vascular access remains the cornerstone of effective hemodialysis treatment. The Tesio catheters has been proposed to be a reliable source of vascular access for the dialysis patients. SUBJECTS AND METHODS: We examined all Tesio catheters inserted over a 3-year period in our hospital. We obtained age, sex, dialysis duration, original nephropaty, vascular access history, complications, dialysis parameters, catheter function duration, confort level for patients and nurses, and death in all our cases. RESULTS: 33 catheters were inserted in 30 patients, 14 male and 16 female. Age 73,92 +/- 9,22 years. Dialysis duration, 25,64 +/- 53,45 months. Diabetic nephropaty 26,66%, NAE 40%, others 33,33%. First vascular access in 13 patients (43,33%), one previously fistula, 5 patients (16,66%), and more of one FAV, 12 patients (40%). We observed two bleeding cases, eight parcial trombosis, one total trombosis (non-function), six tunneled infection and two systemic infection. Only 3 catheters were removal. We obteined good dialysis parameters. Confort state for patients and nurses were satisfactory. Death 12 patients. Catheter function at the moment of study 16,76 +/-12,99 months. CONCLUSIONS: We concluded that Tesio catheters can provide excellent long-term vascular access for hemodialysis patients, especially in the older people and with some previous failure fistulas, with low complication rates and acceptable dialysis parameters and tolerance. However, the arteriovenous fistula remains the gold standard for long-term hemodialysis access.

A Non-inferiority Pilot Study Comparing the Clinical Efficacy and Safety of Generic Wide-spectrum Antibiotic Use in Septic Oncology Patients.

The present study is a non-inferiority study based on a descriptive and comparative case series for comparison of generic vs. original intravenous antimicrobials in septic oncology patients at an oncology private ICU. 1906 cancer patients admitted to Arturo Lopez Perez Foundation, Chile, were included in this study. After recruitment, a first retrospective group of 206 septic cancer patients recorded from 1st January, 2008 until July 14th, 2010, treated with original antibiotics (cefoperazone-sulbactam, imipenem-cilastatin, piperacillin-tazobactam) were included for analyses and a second prospective group of 143 septic cancer patients recorded from July 15th, 2010 until January 02, 2013, treated with the same but generic antibiotics were also included for comparisons. The trial protocol was developed in accordance with Helsinki and Good Clinical Practices recommendations. The results of this study showed no significant differences between the 2 groups in days of treatment, rate of success and lab test determinations (white cell count, PCR and procalcitonin), with lower, but not significant, total bed days and CPU bed days for generic antibiotics. Therefore, we conclude that the safety and efficacy of the generic antibiotics cefactam®, imipen® and Piperazam® are not inferior to original antibiotics for the treatment of severe sepsis in hospitalised patients at the Arturo Lopez Perez Foundation.

Alternate splicing of the shal gene and the origin of I(A) diversity among neurons in a dynamic motor network.

The pyloric motor system, in the crustacean stomatogastric ganglion, produces a continuously adaptive behavior. Each cell type in the neural circuit possesses a distinct yet dynamic electrical phenotype that is essential for normal network function. We previously demonstrated that the transient potassium current (I(A)) in the different component neurons is unique and modulatable, despite the fact that the shal gene encodes the alpha-subunits that mediate I(A) in every cell. We now examine the hypothesis that alternate splicing of shal is responsible for pyloric I(A) diversity. We found that alternate splicing generates at least 14 isoforms. Nine of the isoforms were expressed in Xenopus oocytes and each produced a transient potassium current with highly variable properties. While the voltage dependence and inactivation kinetics of I(A) vary significantly between pyloric cell types, there are few significant differences between different shal isoforms expressed in oocytes. Pyloric I(A) diversity cannot be reproduced in oocytes by any combination of shal splice variants. While the function of alternate splicing of shal is not yet understood, our studies show that it does not by itself explain the biophysical diversity of I(A) seen in pyloric neurons.

Ethnic susceptibility to lung cancer: differences in CYP2E1, CYP1A1 and GSTM1 genetic polymorphisms between French Caucasian and Chilean populations.

Many investigators have reported an association between genetic polymorphisms of cytochromes P-450 CYP2E1, CYP1A1 or glutathione S-transferase Mu (GSTM1) and susceptibility to lung cancer. However, pronounced interethnic variations have been described in the frequencies of these polymorphisms, especially between Asians and Caucasians. The present study was set up to establish CYP2E1 (c1, c2 and C, D), CYP1A1 (m1, m2 and Ile, Val) and GSTM1 (null) allelic frequencies in Chileans (n = 96) who are an admixture of Native Americans and Caucasians (Spaniards). The rare allele frequencies were found to be 0.15 (c2), 0.21 (C), 0.23 (m2), 0.32 (Val) and 0.21 ('null' genotype). These values are significantly higher than those of Caucasians except for the GSTM1 'null' genotype and suggest differences in susceptibility to lung cancer between both populations.

CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people.

CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer patients. In the Chilean healthy group, frequencies of CYP1A1 variant alleles for MspI (m2 or CYP1A1*2A) and ile/val (val or CYP1A1*2B) polymorphisms were 0.25 and 0.33, respectively. Frequencies of variant alleles C (CYP2E1*6) and c2 (CYP2E1*5B) for CYP2E1 were 0.21 and 0.16, respectively and frequency for GSTM1(-) was 0.24. The presence of variant alleles for GSTM1, MspI and Ile/val polymorphisms was more frequent in cases than in controls. However, frequencies for the c2 and C alleles were not significantly different in controls and in cases. The estimated relative risk for lung cancer associated to a single mutated allele in CYP1A1, CYP2E1 or GSTM1 was 2.41 for m2, 1.69 for val, 1.16 for C, 0.71 for c2 and 2.46 for GSTM1(-). The estimated relative risk was higher for individuals carrying combined CYP1A1 and GSTM1 mutated alleles (m2/val, OR=6.28; m2/GSTM1(-), OR=3.56) and lower in individuals carrying CYP1A1 and CYP2E1 mutated alleles (m2/C, OR=1.39; m2/c2, OR=2.00; val/C, OR=1.45; val/c2, OR=0.48; not significant). The OR values considering smoking were 4.37 for m2, 4.05 for val, 3.47 for GSTM1(-), 7.38 for m2/val and 3.68 for m2/GSTM1(-), higher values than those observed without any stratification by smoking. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms could be more susceptible to lung cancer induced by environmental pollutants such as polycyclic aromatic hydrocarbons.

Effect of high ionic strength and inhibitors of H,K-ATPase on the ouabain-sensitive K-p-nitrophenylphosphatase activity in the sea anemone Stichodactyla helianthus.

The ouabain-sensitive, K-stimulated p-nitrophenyl phosphatase (K-pNPPase) activity, an associated activity of the Na,K-ATPase, was assayed in tentacles of the sea anemone Stichodactyla helianthus to investigate the possibility that the sea anemone Na,K-ATPase activity is an associated activity of an H,K-ATPase. Activity was maximal at pH 6.5-7.0, decreasing only slightly in acidic medium but falling abruptly in alkaline medium to 60% of maximum at pH 7.4. The pH of maximum activity was not remarkably altered in high ionic strength medium (560 mM choline chloride), but ouabain-sensitive K-pNPPase activity of both rat and sea anemone was strongly inhibited. Inhibitors of the gastric H,K-ATPase, 100 microM omeprazole and 10 microM SCH 28080, did not inhibit the ouabain-sensitive K-pNPPase activity. Activity of the sea anemone enzyme was inhibited by 10 microM ammonium vanadate, an inhibitor of P-type ATPase, and not by 2.5 mM sodium azide, an inhibitor of both F-type and V-type ATPase. Because the sea anemone K-pNPPase activity was previously found to be more sensitive to ouabain than the Na,K-ATPase activity, K(+)-ouabain antagonism was investigated and found to be relatively muted, whereas K(+)-Na+ competition was stronger than in the rat kidney.

[Acute interstitial nephritis induced by loratadine]. / Loratadina y nefritis intersticial aguda.

Loratadine is a second generation histamine H1 receptor antagonist, that has high potency antiallergic properties and is associated with low adverse effects compared with other antihistamines. Acute interstitial nephritis is a cause of acute renal failure that is most often induced by drugs or, less frequently, infection or sarcoidosis. Although the number of drugs associated with acute intersticial nephritis is too large, the antihistaminic loratadine have never been reported before. We report a case of an interstitial nephritis with acute renal failure that suggesting hypersensitivity reaction in a 77 old man who had received loratadine (10 mg/day) during ten days before his assessment to our hospital by disseminated pruritic syndrome. The initial suspect was rapidly progressive glomerulonephitis and renal biopsy was practice and treatment with corticosteroids were initiated (prednisone bolus of 500 mg three days and 1 mg/kg/day/later). The loratadine therapy was cessation. He exhibiting a slow and progressive improvement on renal function and one month later, urea and creatinine levels was normal and hematuria and proteinuria had disappeared. The corticosteroids therapy were progressive decreased until withdrawal. We think that this is an interesting case, basing in its clinical presentation and that it had never been reported before.

Delphinol® standardized maqui berry extract reduces postprandial blood glucose increase in individuals with impaired glucose regulation by novel mechanism of sodium glucose cotransporter inhibition.

AIM: The impetus of our study was to investigate the effects of a nutritional supplement Delphinol®, an extract of maqui berries (Aristotelia chilensis) standardised to ≥25% delphinidins and ≥35% total anthocyanins, on postprandial blood glucose and insulin levels and identify the physiologic mechanism involved. METHODS: Postprandial blood glucose and insulin were investigated in double-blind, placebo-controlled, cross-over fashion in ten volunteers with moderate glucose intolerance. Longer term effects on blood sugar levels were investigated in streptozotocin-diabetic rats over a four months period. Effects of maqui berry delphinidins on sodium-glucose symport were examined in rodent jejenum of the small intestine. RESULTS: Delphinol® intake prior to rice consumption statistical significantly lowered post prandial blood glucose and insulin as compared to placebo. We identified an inhibition of Na+-dependant glucose transport by delphinidin, the principal polyphenol to which Delphinol® is standardised. In a diabetic rat model the daily oral application of Delphinol® over a period of four months significantly lowered fasting blood glucose levels and reached values indistinguishable from healthy non-diabetic rats. CONCLUSION: Our results suggest a potential use of Delphinol® for naturally controlling post-prandial blood glucose owed to inhibition of sodium glucose co-transporter in small intestine.

Bioequivalence of acenocoumarol in chilean volunteers: an open, randomized, double-blind, single-dose, 2-period, and 2-sequence crossover study for 2 oral formulations.

The aim of this study was to compare the bioavailability of an oral formulation of the coumarin derivative-vitamine K antagonist acenocoumarol (Acebron™ 4 mg, Test) with the reference formulation (Neo-Sintrom™ 4 mg). We performed a single-dose, double-blind, fasting, 2-period, 2-sequence, crossover study design. Plasma concentrations of acenocoumarol were determined using a validated UPLC-MS/MS method. 24 healthy Chilean volunteers (11 male, 13 female) were enrolled and all of them completed the study. Adverse events were monitored throughout the study. The values of the pharmacokinetic parameters were (mean ± SD): AUC0-24 =1 364.38±499.26 ngxh/mL for the test and 1 328.39±429.20 ngxh/mL for the reference; AUC0-∞ =1 786.00±732.85 ngxh/mL for the test and 1 706.71±599.66 ngxh/mL for the reference; Cmax =180.69±35.11 ng/mL with a Tmax of 1.83±0.95 h for the test and 186.97±38.21 ng/mL with a Tmax of 2.19±0.83 h for the reference. Regarding half life measurements, the mean ± SD of t1/2 were 11.84±4.54 h for the test and 11.08±3.28 h for the reference. The 90% confidence intervals for the test/reference ratio using logarithmic transformed data were 97.89-100.87%, 98.62-101.99% and 98.64-102.38% for Cmax, AUC0-t(24) and AUC0-∞. There were no significant differences in pharmacokinetic parameters between groups.The results obtained in this study lead us to conclude, based on FDA criteria, that the test acenocoumarol formulation (Acebron™, 4 mg tablets) is bioequivalent to the reference product (Neo-Sintrom™, 4 mg tablets).