Alejandra Toledo López

Reliable method for the determination of ranitidine by liquid chromatography using a microvolume of plasma.

Abstract The aim of the present study was to develop a simple method to measure ranitidine, using 100 μl of plasma, by high-performance liquid chromatography with a Symmetry C 18 column and UV detection at 313 nm. Linearity was assessed in the range from 50 to 1500 ng ml −1 and had a correlation coefficient of 0.999. The inter- and intra-day coefficients of variation were less than 7%. The limits of detection and quantitation were 5 and 15 ng ml −1 , respectively. Drug levels were determined satisfactorily in three patients. A simple and reliable method was developed which uses a microvolume of plasma, particularly useful in low-weight children.

Effects of gender and phase of the menstrual cycle on the kinetics of ranitidine in healthy volunteers.

The present study was undertaken to determine if differences exist in the pharmacokinetic parameters of oral ranitidine caused by gender and stage of the menstrual cycle. The study was performed in two steps, in the first a pharmacokinetic study was performed on 10 men (average age 35.5 yrs) and 10 women (average age 34.7 yrs) during the follicular phase, and in the second the pharmacokinetic study was performed only on the same women in their luteal phase. Subjects received a tablet dose of 300 mg ranitidine, and blood samples were drawn at several times after its ingestion. Plasma ranitidine concentration was determined by high performance liquid chromatography. Comparison of the pharmacokinetic parameters of women and men revealed statistically significant differences both in distribution volume (Vd) with values of 2.0 and 6.3 l/kg, Area Under Curve (AUC) with values of 7312.15 and 11471.94 ng/ml/h, and clearance (CLt) with values of 0.65 and 0.59 l/kg/h, respectively. Several pharmacokinetic parameters in women were different in the follicular compared to the luteal phase; for example, Vd was 2.0 and 5.6 l/kg, AUC was 7312.15 and 5195.83 ng/ml/h, and CLt was 0.65 and 0.97 l/kg/h, in the respective phases. Moreover, the maximum concentration (Cmax) was 1086 ng/ml in the follicular vs. 864 ng/ml in the luteal phase. The first study detected differences between men and women in several pharmacokinetic parameters, mainly those indicative of drug availability, for example, Vd, AUC, and CLt. Comparison of data obtained in the follicular phase with those obtained in the luteal phase revealed differences in most pharmacokinetic parameters, which is seemingly indicative of the characteristic physiological changes associated with the luteal phase that largely affect the kinetics and availability of drugs such as ranitidine. Although it has been postulated that hormonal fluctuation within the menstrual cycle phase is the primary cause of documented gender differences in the pharmacokinetics and pharmacodynamics of drugs, further study of related factors is required to fully understand how gender and menstrual cycle rhythms affect the pharmacokinetic process in their entirety.

Cinitapride protects against ethanol-induced gastric mucosal injury in rats: role of 5-hydroxytryptamine, prostaglandins and sulfhydryl compounds.

This study was designed to determine the gastroprotective properties of cinitapride (CNT), a novel prokinetic benzamide derivative agonist of 5-HT4 and 5-HT1 receptors and 5-HT2 antagonist, on mucosal injury produced by 50% (v/v) ethanol. Results were compared with those for 5-hydroxytryptamine (5-HT: 10 mg kg-1). The possible involvements of gastric mucus secretion, endogenous prostaglandins (PGs) and sulfhydryl compounds (SH) in the protection mediated by CNT were also examined. Intraperitoneal administration of CNT (0.50 and 1 mg kg-1), 30 min before ethanol, significantly prevented gastric ulceration and increased the hexosamine content of gastric mucus. CNT (1 mg kg-1) also produced a significant increase in gastric mucosal levels of PGE2, but did not induce any significant changes in SH values. On the contrary, pretreatment with 5-HT worsened ethanol-induced erosions, however, did not affect gastric mucus secretion, glycoprotein content or PGE2 levels, although the non-protein SH fraction was significantly decreased. The present results demonstrate that the gastroprotective effects of CNT could be partly explained by a complex PG dependent mechanism. We suggest that 5-HT dependent mechanisms through 5-HT2 receptor blockade and 5-HT1 receptor activation could be also involved.

Ulcer-protecting effects of a flavonoid fraction from Bidens aurea. Role of endogenous prostaglandins and microvascular permeability.

This study was designed to determine the ulcer-protecting effects of a flavonoid fraction obtained from the flowers of Bidens aurea (Aiton) Sherff against gastric lesions induced by absolute ethanol. The possible involvement of gastric mucus secretion, endogenous prostaglandins (PGs) and mucosal microvascular permeability (MVP) in the protection mediated by the flowers of B. aurea were also determined. Flavonoid fraction pretreatment (250 mg/kg) 120 min before absolute ethanol was most effective in necrosis prevention. There was also a marked increase (p < 0.001) in hexosamine content. Intraperitoneal administration of indomethacin (IND) (10 mg/kg) partially inhibited gastric protection and the values of PGE(2) were significantly (p < 0.001 and p < 0.05) augmented. In addition, administration of 250 mg/kg of the extract reduced the elevated MVP induced by alcohol in rat gastric mucosa. These results demonstrate that the gastroprotective effects of B. aurea flowers could be partly explained through a complex prostaglandin-dependent mechanism involving stimulation of mucus glycoprotein content and reduction of MVP values.

HEALING PROCESS INDUCED BY A FLAVONIC FRACTION OF BIDENS AUREA ON CHRONIC GASTRIC LESION IN RAT. ROLE OF ANGIOGENESIS AND NEUTROPHIL INHIBITION

Absrtract The aim of this study was to elucidate the mechanism of the healing process mediated by the flavonic fraction of Bidens aurea on chronic gastric ulceration induced by 5% acetic acid in rats. The diethyl ether extract (125 and 62.5 mg kg- 1 body weight) was administered in a single doses, 7 and 14 days after provocation of lesions. Our results demonstrated that both doses significantly decreased the macro and microscopic ulcer index. Usually after 14-days treatment the lesions were found completely covered with regenerative epithelium and also an important proliferation of blood vessels was observed. Myeloperoxidase (MPO) activity was assayed and used as an index of leucocyte infiltration. Application of acetic acid produced a significant increase of this activity 7 days after induction of chronic injury. Administration of 125 mg kg -1 of the ether extract provoked a sharp reduction on the enzymatic activity at the same period. After 14 days, this decrease was higher with both doses (p<0.001). In addition, the macroscopic examination showed a drastic reduction of leucocyte infiltration in treated groups. These results suggest that the recovery of vascularization of the ulcerated area and the decrease of neutrophil infiltration are involved in the antiulcerogenic effect of the flavonoid fraction of Bidens aurea.

Patterns of drugs prescribed concomitantly with levothyroxine in children with hypothyroidism

The aim of this work was to know the prescription pattern of drugs for the treatment of concomitant pathologies in children with hypothyroidism, who were receiving levothyroxine, so as to identify drugs with possible interaction risk and avoid the production of adverse effects. An analysis of treatments in children diagnosed of hypothyroidism treated with levothyroxine and medicines added for the treatment of concomitant pathologies in an endocrinology service from December 1999 to December 2009 was carried out. For capturing the information, a form for information gathering was used and the Naranjo causality algorithm was used. 475 clinical files corresponding to 292 (61.47%) females and 183 (38.53%) males were reviewed. The concomitant pathologies most frequently seen were gastrointestinal (60.47%) and respiratory diseases with 55.58%. The number of drugs simultaneously administered with levothyroxine was from 1 to 7. Applying the Naranjo algorithm, 38.5% were adverse drug reactions (ADRs) definite, 23% ADRs probable, 23% ADRs possible and 4% doubtful. In conclusion, the prescription of drugs co-administered simultaneously with levothyroxine should be done in a rational form because there are drugs as anticonvulsant, diuretics or gastrointestinal that can interact between them as with levothyroxine, principally with drugs administered in a chronic form.