High-Fat Breakfast Increases Bioavailability of Albendazole Compared to Low-Fat Breakfast: Single-Dose Study in Healthy Subjects.

Purpose: Albendazole is a benzimidazole carbamate drug with anthelmintic and antiprotozoal activity against intestinal and tissue parasites. It has been described that the administration with meals increases albendazole absorption. Our aim was to compare the systemic exposure in healthy volunteers of two albendazole formulations after a single oral dose under fed conditions and to evaluate the effect of breakfast composition on albendazole and albendazole sulfoxide bioavailability. Methods: 12 healthy volunteers were included in a 4-period, 4-sequence, crossover, open, randomized, bioequivalence clinical trial, including two stages to compare two formulations of albendazole. Single oral doses of 400 mg albendazole were administered under fed conditions (a low-fat breakfast in first stage and a high-fat breakfast in the second) separated by 7-day washout periods. Plasma albendazole and albendazole sulfoxide concentrations were measured by HPLC-MS/MS. Findings: Albendazole absorption was clearly influenced by the meal composition. A high-fat breakfast increased albendazole and albendazole sulfoxide area under the concentration-time curve (AUC) and maximum concentration (Cmax) by double, compared to a low-fat breakfast. The bioavailability of the two formulations was very similar, although the sample size was not sufficient to demonstrate bioequivalence because the intraindividual variability of albendazole was approximately 60%. Implications: The higher albendazole and albendazole sulfoxide levels when administered with a high-fat meal could be of importance in clinical practice. Since albendazole labeling recommends its administration with meals, it is necessary to insist on taking it with a fatty meal so that the effectiveness of albendazole is not compromised.

Evaluation of the Relationship Between Pharmacokinetics and the Safety of Aripiprazole and Its Cardiovascular Effects in Healthy Volunteers.

AIMS: The aim of this study was the evaluation of the possible relationship between pharmacokinetics and the safety of aripiprazole as well as its influence on blood pressure (BP), heart rate (HR), and corrected QT (QTc) interval. METHODS: The study population comprised 157 healthy volunteers from 6 bioequivalence clinical trials. Subjects were administered a single 10-mg oral dose of each formulation separated by a 28-day washout period. Plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry. Blood pressure was measured at the following times: predose and 0.5, 2, 4, 6, and 8 hours postdose. An electrocardiogram was recorded at predose, 4, and 8 hours postdose. RESULTS: Area under the curve (AUC), maximum plasma concentration, half-life, and distribution volume corrected for weight were higher in women. Aripiprazole treatment produced a decrease of BP (9.3 mm Hg on systolic and 6.2 mm Hg on diastolic pressure) and an increase in HR (12.1 beats per minute) and QTc interval (9.1 milliseconds). There were sex differences in BP, HR, and QTc interval. Women and subjects with higher AUC and maximum plasma concentration values were more prone to experience adverse drug reactions and gastrointestinal adverse reactions. The AUC was related with systolic BP and diastolic BP decrease and HR increase but there was no relationship between aripiprazole concentrations and QTc increase. CONCLUSIONS: Aripiprazole decreases BP and increases HR and QTc interval. Pharmacokinetics, pharmacodynamics, and safety of aripiprazole are affected by sex. There is a directly proportional relationship between pharmacokinetic parameters and adverse drug reactions and effect on BP and HR.

Evaluation of the relationship between polymorphisms in CYP2C19 and the pharmacokinetics of omeprazole, pantoprazole and rabeprazole.

AIM: To evaluate the possible association between polymorphisms in CYP2C19 and the pharmacokinetics of omeprazole, rabeprazole and pantoprazole. MATERIALS & METHODS: 151 healthy volunteers were evaluated for polymorphisms in the CYP2C19 gene using real-time polymerase chain reaction. Plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry. RESULTS: Carriers of the *2 allele displayed poor metabolism for all the PPIs studied (around 50% decrease in clearance). Subjects with the *17 allele showed a light increase in clearance compared with *1/*1 (not significant). CONCLUSION: CYP2C19*2 is associated with decreased clearance of all the PPIs, that could be associated with higher drug efficacy. CYP2C19*17 could increase clearance of these drugs, although the effect seems small.

Evaluation of the relationship between polymorphisms in CYP2C8 and CYP2C9 and the pharmacokinetics of celecoxib.

Celecoxib is metabolized by enzymes of the cytochrome P450 (CYP450) superfamily, mainly CYP2C9 and CYP3A4. Polymorphisms in the CYP2C9 gene have been associated with decreased enzyme activity and alteration of celecoxib pharmacokinetic parameters. However, literature reports are limited, and some results are contradictory. We enrolled 24 healthy volunteers in a single-dose replicated crossover trial with celecoxib 200 mg. We evaluated the association between single-nucleotide polymorphisms in the CYP2C8 and CYP2C9 genes (CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP2C9*2, and CYP2C9*3) of these individuals and the pharmacokinetic parameters of celecoxib. Subjects carrying CYP2C9*1/*3 and CYP2C9*3/*3 had a higher AUC (2- and 7.7-fold, respectively) and Cmax (1.5- and 1.8-fold, respectively) and lower clearance (2.3- and 10-fold, respectively) than those carrying CYP2C9*1/*1. Half-life was 2.7-fold higher in subjects with CYP2C9*3/*3 than in those with the wild type but not in those with CYP2C9*1/*3. We did not find any significant effect of gender or CYP2C8 polymorphisms on the pharmacokinetics of celecoxib. In conclusion, the recommended dose of celecoxib should be decreased in CYP2C9*3 carriers, especially in homozygous subjects.

Tratamiento correctivo para un conducto protésico anormalmente ensanchado / Corrective treatment for a prosthetic conduct abnormally widened

La caries radicular del conducto protésico de piezas dentarias pilares determina la repetición de su restauración. Una vez desalojada la restauración, nos enfrentamos a la necesidad de remover grandes cantidades de dentina cariada o infiltrada. Al eliminarla dejamos un conducto protésico exesivamente ensanchado. Documentada la necesidad de restituir el tejido dentinario perdido, es que se propone una técnica correctiva y de refuerzo utilizando Vitremer Material de Restauración (3M), que se aplicó en 10 casos y ha probado ser exitoso al mediano plazo (un año)

Modificación músculo esqueletal de la técnica de impresión miofuncional para extremo libre mandibular / Muscle skeletal modification of the impression technique for mandibular distal extension

La técnica de impresión para extremo libre mandibular ha sufrido una evolución importante a lo largo del tiempo, producto de la incorporación de nuevos niveles de funcionalidad. Es así como la técnica de Applegate, fue modificada por Mc Craken, y ésta a su vez fue mejorada por la Técnica de Impresión a Boca Cerrada Miofuncional, incorporando el 3er nivel de funcionalidad de flancos externos vestibulares y linguales determinados por las matrices funcionales labio lengua y mejilla. La finalidad del presente artículo es presentar y desarrollar una técnica que incorpora una nueva variable que dice relación con los momentos de flexión mandibular que se producen, a la luz de recientes investigaciones, durante la fase oclusal del ciclo masticatorio y la correcta utilización de los materiales empleados en la evolución de la técnica y construcción de la base protésica

Estudio del fracaso de la pieza pilar endodónticamente tratada en rehabilitación oral / Study of the failure of the endodontically treated teeth in oral rehabilitation

Los pilares dentarios endodónticamente trarados son de gran utilización en odontología. La finalidad del presente artículo es analizar y entregar una pauta para prevenir fracasos mediatos de la PPET. Se realizó un estudio longitudinal de los fracasos clínicos evaluados en la Escuela de Graduados de la Facultad de Odontología de la Universidad de Chile. Pacientes que concurren a control y mantención rehabilitados en el Programa de Especialización en Rehabilitación Oral con mención en prótesis desde 1988 a la fecha (50 casos)

Ataches de semiprecisión / Semiprecision attachments

Este artículo presenta una visión histórica de los ataches de semiprecisión y de sus características principales. Se efectúa un análisis descriptivo en que se les clasifica de acuerdo a diferentes criterios y se mencionan sus indicaciones y contraindicaciones. Además se les compara con los sistemas de retención de tipo convencional y con los ataches de precisión