Use of botulinum toxin type a before abdominal wall hernia reconstruction.

BACKGROUND: Abdominal wall hernia repair after open abdomen management represents a surgical challenge, particularly due to muscle tension and lateral retraction. This study was designed to propose the use of Botulinum Toxin Type A (BTA) before abdominal wall hernia repair. METHODS: A prospective study of patients with abdominal wall hernia after open abdomen management was undertaken between September 2007 and January 2009. Bilateral BTA application was performed under electromyographic guidance at the abdominal wall. Transverse abdominal wall defect measurement was practiced at weekly intervals: clinically, in the first two patients, and with CT scan in the following 10 patients. Surgical closure was scheduled if no further hernia defect reduction was noted. Patients were followed at monthly hospital visits. RESULTS: In the first two patients, a hernia defect reduction of 50 and 47.2%, respectively, was documented by the third week after BTA application, with no further reduction. In the 10 patients under CT scan hernia defect measurement, when comparing the initial mean transverse defect measure and at 4 weeks after BTA application (13.85 +/- 1.49 cm vs. 8.6 +/- 2.07 cm), an overall mean reduction of 5.25 +/- 2.32 cm was observed (p < 0.001; 95% confidence interval, 3.59-6.91). Hernia repair was performed, with no recurrences at a mean follow-up of 9.08 months. CONCLUSIONS: BTA application before abdominal wall hernia repair seems to be useful. The lateral muscles paralysis achieved and transverse hernia defect reduction allows a minimal tension closure. To our knowledge, this is the first report of BTA application before abdominal wall hernia reconstruction.

Comparative bioavailability of two oral formulations of omeprazole.

Omeprazole is a very widely used proton-pump inhibitor. Currently, there are several branches available in Mexico, however, limited information about their bioavailabilities is available. The purpose of this study was to compare the bioavailability of two of them, Losec and Omelcid. Twenty-eight healthy volunteers were enrolled in this study that was carried out following the recommendations of the Declaration of Helsinki. Subjects read the protocol that was approved by the institutional research and ethics committees and gave written consent for participation. After an overnight fast, volunteers received an oral dose of 20 mg omeprazole (formulation A or B) and blood samples were obtained at selected times during 8 hours. Plasma was obtained by centrifugation and stored frozen until analyzed by a validated HPLC method. Pharmacokinetic parameters were obtained by non-compartmental analysis and values (+/- s.e.m.) obtained were as follows: Cmax 354.28 +/- 51.57 and 308.95 +/- 44.42 ng/ml, t(max) 2.26 +/- 0.22 and 2.63 +/- 0.24 h and AUC(8h) 701.01 +/- 109.34 and 774.13 +/- 132.84 ngh/ml for formulations A and B respectively. Log transformed Cmax and AUC(8h) were compared by analysis of variance and 90% confidence limits of the parameters ratios (B/A) were 72.73-106.34% and 90.32-124.96%, for Cmax and AUC(8h) respectively. As confidence intervals did not exceed the 70-142.9% limits for Cmax and 80-125% for AUC(8h), it is concluded that the formulations tested are bioequivalent.

Isobolographic analyses of the gabapentin-metamizol combination after local peripheral, intrathecal and oral administration in the rat.

This study was designed to evaluate the possible antinociceptive interaction between gabapentin and metamizol on formalin-induced nociception. Gabapentin, metamizol or a fixed dose-ratio combination of both drugs were assessed after local peripheral, intrathecal and oral administration in rats. Isobolographic analyses were employed to define the nature of the interaction between drugs. Gabapentin, metamizol and gabapentin-metamizol combinations yielded a dose-dependent antinociceptive effect when administered by the three different routes. ED30 values were estimated for the individual drugs and isobolograms were constructed. Theoretical ED30 values for the combination estimated from the isobolograms were 21.11 +/- 1.17 microg/paw, 104.6 +/- 5.5 microg/rat and 78.8 +/- 5.5 mg/kg for the local peripheral, intrathecal and oral administration routes, respectively. These values were significantly higher than the experimentally obtained ED30 values which were 11.3 +/- 1.5 microg/paw, 36.8 +/- 3.1 microg/rat and 15 +/- 1.2 mg/kg indicating a synergistic interaction. Systemic administration resulted in the highest synergism. Data confirm that low doses of the gabapentin and metamizol can interact synergistically to reduce formalin-induced nociceptive behavior suggesting that this combination could be useful to treat inflammatory pain in humans.

Bioequivalence of two oral formulations of glyburide (glibenclamide).

Glyburide (glibenclamide) is a sulfonylurea derivative that is very widely used in the treatment of type II diabetes mellitus. Currently, there are several pharmaceutical formulations available in Mexico containing this drug, however, very limited information about their bioavailabilities is known. The purpose of this study was to compare the bioavailability of two formulations of glyburide used in Mexico, Daonil and Gen-Glybe. Twenty-four Mexican healthy volunteers participated in this study that was carried out following the recommendations of the Declaration of Helsinki. Subjects received a dose of 10 mg of glyburide (two tablets of 5 mg) under fasting conditions in two separate sessions using a randomized crossover design with a one week washout period. Plasma samples were obtained at selected times over 24 hours and stored frozen until analyzed. Pharmacokinetic parameters were obtained and values (mean +/- S.E.M.) were as follows: Cmax 273.32 +/- 25.84 versus 294.83 +/- 27.12 ng/ml; tmax 3.03 +/- 0.23 versus 2.87 +/- 0.24 h; and AUC24h 1396.66 +/- 130.18 versus 1557.99 +/- 140.24 ng x h/ml, for Daonil and Gen-Glybe tablets, respectively. Pharmacokinetic parameters were compared using analysis of variance for a cross-over design and ratios of AUC24h and Cmax and 90% confidence intervals were obtained. As confidence intervals did not exceed the limits of acceptance (80--125%) for Cmax and AUC24h, it is concluded that the formulations tested are bioequivalent.

Comparative bioavailability of two oral suspensions of naproxen sodium.

The bioavailability of naproxen sodium (CAS 26159-34-2) after administration of two oral suspensions, reference or test (Pactens), was compared in 24 healthy subjects. The volunteers received an oral dose of 250 mg (10 ml) in two separate sessions under fasting conditions according to a randomized cross-over design and blood samples were obtained at selected times for a period of 72 h. Plasma samples were analyzed by a high-performance liquid chromatographic method for determination of naproxen. Individual plasma concentration against time curves were constructed and pharmacokinetic parameters were obtained by non-compartmental techniques. The parameters obtained (mean +/- S.E.M.) were: C(max) 43.93 +/- 1.83 and 44.91 +/- 2.15 microg/ml, t(max) 2.38 +/- 0.21 and 1.83 < or = 0.19 h, AUC(72 h) 721.73 +/- 18.47 and 722.55 +/- 19.07 microg x h/ml for reference and test formulations, respectively. Maximal concentration, AUC(72 h) and AUC(infinity). were log transformed and compared by analysis of variance and ratios; in addition, 90% confidence limits were obtained. As confidence limits were included in the 80-125% range and the probability of exceeding these intervals was always lower than 0.05, it is concluded that the formulations tested are bioequivalent.

Comparative bioavailability of two oral formulations of ranitidine.

The current requirement of the Mexican Authorities to demonstrate the interchangeability of ranitidine formulations is to establish that the dissolution profile of the drug shows similarity. In order to establish if this requirement is adequate, the bioavailability of two formulations that did not meet this similarity were compared. Twenty-five female volunteers received 150 mg ranitidine (Azantac or Midaven) under fasting conditions in two separate sessions using a cross-over design. Plasma samples were obtained at selected times for a period of 12 h and stored frozen at -80 degrees C until analysed. Ranitidine plasma levels were determined and pharmacokinetic parameters were obtained. Values (mean+/-SEM) were: Cmax 528.85+/-25.34 and 563.03+/-33.25 ng/ml, tmax 2.76+/-0.19 and 2.79+/-0.18 h, and AUC12 h 2694.94+/-99.50 and 2648.51+/-133.38 ng.h/ml, for Azantac or Midaven, respectively. No statistically significant difference was obtained in the parameters evaluated. Moreover, 90% confidence limits were 96.6%-116.2% and 90.7%-105.1% for Cmax and AUC12 h ratios, respectively, indicating that the formulations tested are bioequivalent, despite the dissimilarity in the dissolution profile of the formulations. These results suggest that the comparative dissolution profile is not an adequate test to demonstrate the interchangeability of ranitidine formulations.

Synergistic interaction between gabapentin and metamizol in the rat formalin test.

The purpose of this study was to assess the possible synergistic interaction between gabapentin and metamizol in the rat formalin test. Female Wistar rats were injected into the dorsal surface of the right hind paw with 50 microl of diluted formalin (1%). Formalin injection induced a typical flinching behavior indicating nociception. Reduction of the number of flinches was considered as antinociception. Gabapentin (10-300 mg/kg), metamizol (30-600 mg/kg), or the combination of gabapentin and metamizol were administered orally and the antinociceptive effect in the formalin test was determined. Isobolographic analyses were used to define the nature of the functional interaction between gabapentin and metamizol in a fixed-dose ratio (0.5:0.5). Gabapentin (ED30 18.3+/-7.9 mg/kg), metamizol (ED30 139.2+/-6.2 mg/kg) and fixed-dose ratio gabapentin-metamizol combinations dose-dependently reduced flinching behavior during second phase of the test. Theoretical ED30 value for the combination estimated from the isobologram was 78.8+/-5.5 mg/kg, whereas that experimental ED30 value was 15.0+/-1.2 mg/kg. Results indicate that oral administration of gabapentin and metamizol can interact synergistically to reduce inflammatory pain in the formalin test and suggest the use of this combination to relieve pain in humans.

Pharmacokinetics of oral ranitidine in Mexicans

The pharmacokinetics of oral ranitidine were studied in 24 Mexican male healthy volunteers. Subjects received a tablet containing 150 mg of ranitidine (Azantac TM, Glaxo de Mexico, Mexico, City) after an overnight fast and blood samples were drawn at several times for a period of 24 h. Ranitidine concentration in plasma was measured by high performance liquid chromatography and pharmacokinetic parameters were determined by non-compartmental analysis. Ranitide plasma concentration increased with time, reaching a maximum of (mean ñ SEM) 484 ñ 34 ng/ml in 2.7 ñ 0.2 h. Plasma levels then decayed with a terminal half-life of 4.8 ñ 0.3 h. The area under the plasma concentration against time curve was 2440 ñ 126 ngh/ml. Oral ranitidine pharmacokinetic parameters in mexicans appeared to be similar to those previously reported for caucasians

Efectos del aguacate sobre los niveles de lípidos séricos en pacientes con dislipidemias fenotipo II y IV / Effects of avocado plasma lipid concentrations in patients with hypercholesterolemia

Para examinar el efecto del aguacate sobre los niveles de lípidos séricos en pacientes dislipidémicos, se incluyeron a 8 sujetos con dislipidemia fenotipo IV y 8 del fenotipo II en un estudio dietético, en un modelo cruzado en el que se compararon dos dietas: una dieta rica en ácidos grasos monoinsaturados (DRCA), en la que el aguacate fue su principal fuente (30 por ciento de calorías totales como grasas y de ellas 75 por ciento del aguacate), con restricción de grasas saturadas y menos de 300 mg de colesterol por día. La otra fue una dieta baja en grasas saturadas y en grasa total, sin aguacate (DRSA). Ambas dietas duraron 4 semanas y su orden fue asignado aleatoriamente. Los pacientes realizaron sus tres alimentos en el comedor de nuestra unidad. Tanto la DRCA como la DRSA redujeron significativamente los niveles de colesterol total y colesterol-LDL sólo en el fenotipo II. En el fenotipo IV, la DRCA produjo un descenso moderado de los triglicéridos, mientras que la DRSA incrementó sus niveles. La DRCA produjo un importante incremento en los niveles de colesterol-HDL en ambos fenotipos, mientras que la DRSA sólo lo hizo en el fenotipo II. El aguacate es una excelente fuente de ácidos grasos monoinsaturados, y puede utilizarse dentro de los planes dietéticos de manejo de los pacientes con dislipidemias, con ventajas sobre las dietas más bajas en grasa total y con mayor cantidad de carbohidratos

Determination of oral rifampin pharmacokinetic parameters in Mexicans and comparison with other populations: absence of evidence for interethnic variability

Oral pharmacokinetics of rifampin were studied in eight Mexican young healthy male volunteers after administration of a 600 mg oral dose. After and overnight fast, subjects received medication and blood samples were drawn at selected time over a 24-h period. Rifampin plasma levels were determined by HPLC. Pharmacokinetic parameters (mean ñ SEM) were: Cmax 13.514 ñ 1.775 µg/ml, tmax 1.88 ñ 0.30 h, AUC 73.61 ñ 9.48 µg.h/ml anf half-life 2.98 ñ 0.29 h. Results were compared with those obtained for the other populations under similar conditions in order to explore the possibility of interethnic variability, since it has been reported that rifampin pharmacokinetics in Indonesian subjects differ from those found in Europeans. Pharmacokinetic data found in Mexican were comparable with those observed in Brithis, Indian, Japanese and Italian individuals. As the parmacokinetics of rifampin seem to be similar different populations, it is concluded that ethnic origin does not a appear to play and important role. Therefore, dosing regimens designed for Caucasians can be extrapolated for other populations