Relative bioavailability of new formulation of paracetamol effervescent powder containing sodium bicarbonate versus paracetamol tablets: a comparative pharmacokinetic study in fed subjects.

OBJECTIVE: the aim of this relative bioavailability study was to determine the rate and extent of absorption of Alikal Dolor (effervescent powder containing paracetamol 500 mg/sodium bicarbonate 2318 mg)--test formulation (T) in relation to Parageniol (paracetamol 500 mg coated tablets)--reference formulation (R). METHODS: 18 healthy volunteers (10 male and 8 female aged between 21 and 46 years) received, after 2 h of standardized breakfast, a single oral dose with 220 ml of water, in an open, randomized, crossover study, with a 7-day wash-out period. Paracetamol concentrations were established at 0, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 75, 90 min and at 2, 4, 6, 8 and 10 h postdose by HPLC with an ultraviolet detector. RESULTS: the regression coefficient determined for paracetamol calibration curves was 0.9983 +/- 0.0034 and the working range was from 0.2 to 50 microg/ml. The quantification limit was 0.2 microg/ml. The rate of absorption was significantly greater (p < 0.03) for T (T(max) = 20.4 min) compared with R (T(max) = 38.4 min). Extent of absorption over the first 30 min postdose AUC((0-30 min)) was 4.21-fold greater (p < 0.03) for T compared with R, without differences between C(max.) The 90% CI on the geometric mean for C(max), AUC((0-10 h)) and AUC((0-)) ratios (T/R) were within the limits of 0.80-1.25, indicating both formulations were bioequivalent with respect to these parameters. CONCLUSION: paracetamol was absorbed at least twice as fast from T-containing sodium bicarbonate compared with R. This pharmacokinetic feature could prove crucial from the therapeutic point of view as it would allow a lower latency in the action time of paracetamol in producing its analgesic and antithermal effect.

Effects of a single low dose of ranitidine and effervescent antacids on intragastric acidity in healthy volunteers.

INTRODUCTION/AIMS: We hypothesized that a combination of an effervescent antacid and ranitidine could allow immediate and long-lasting increase intragastric acidity. Our aim was to determine the effect of the combined intake of both, of a low dose ranitidine (OTC) and 5 g of antacid on gastric pH. MATERIAL AND METHODS: Twenty healthy Helicobacter pylori negative volunteers were enrolled. The study consisted in a fasting 6-hour gastric ph-metric procedure performed in two different periods: baseline (1-hour before drug) and post-drug (5-hours) after oral administration of a single dose of ranitidine (75 mg) plus 5 g of a commercial composed alkaline (sodium bicarbonate, citric acid, sodium carbonate). RESULTS: While two subjects did not complete the pH-metry analysis due to technical reasons, 18 volunteers were finally assessed. Baseline intragastric pH (1.3 +/- 0.1) (mean +/- SD) rose significantly after administration of the drug (mean pH value for the whole period: 5.1 +/- 0.3; p<0.00001). The pH increased after administration of the study combination and values higher than pH 3 and pH 4 were reached immediately (median time: 27 sec, range: 0-189 and 54 sec, range 27-3,600 sec, respectively). Gastric pH was initially maintained above 4 for 23.0 +/- 5 minutes. The mean time lapsed with pH < 4 during the post-drug period was 96 +/- 17 min (32% ofthe total time). CONCLUSION: Our study confirms the fast and persistent effect produced by the administration of a combination of antacid salts plus low dose of ranitidine. We suggest that the given combination could be effective, fast and safe for sporadic pyrosis or mild grastroesophageal reflux symptoms.

Effects of a single low dose of ranitidine and effervescent antacids on intragastric acidity in healthy volunteers / Efectos de bajas dosis de ranitidina y antiácidos efervescentes sobre la acidez intragástrica en voluntarios sanos

Introduction/aims: We hypothesized that a combination of an effervescent antacid and ranitidine could allow immediate and long-lasting increase intragastric acidity. Our aim was to determine the effect of the combined intake of both, of a low dose ranitidine (OTC) and 5g of antacid on gastric pH. Material and methods: Twenty healthy Helicobacter pylori negative volunteers were enrolled. The study consisted in a fasting 6-hour gastric ph-metric procedure performed in two different periods: baseline (1-hour before drug) and post-drug (5-hours) after oral administration of a single dose of ranitidine (75 mg) plus 5 g of a commercial composed alkaline (sodium bicarbonate, citric acid, sodium carbonate). Results: While two subjects did not complete the pH-metry analysis due to technical reasons, 18 volunteers were finally assessed. Baseline intragastric pH (1.3±0.1) (mean±SD) rose significantly after administration of the drug (mean pH value for the whole period: 5.1±0.3; p<0.00001). The pH increased after administration of the study combination and values higher than pH 3 and pH 4 were reached immediately (median time: 27 sec, range: 0- 189 and 54 sec, range 27-3,600 sec, respectively). Gastric pH was initially maintained above 4 for 23.0±5 minutes. The mean time lapsed with pH<4 during the post-drug period was 96±17 min (32% of the total time). Conclusion: Our study confirms the fast and persistent effect produced by the administration of a combination of antacid salts plus low dose of ranitidine. We suggest that the given combination could be effeceffective, fast and safe for sporadic pyrosis or mild grastroesophageal reflux symptoms.

Introducción/objetivos: la combinación de un antiácido efervescente y ranitidina podría brindar un descenso inmediato y prolongado de la acidez intragástrica. Nuestro objetivo fue determinar el efecto de la ingesta conjunta de ambos (75 mg de ranitidina y 5 g de antiácidos) sobre el pH gástrico. Material y métodos: se incluyeron 20 voluntarios sanos, con anticuerpos anti- Helicobacter pylori negativos. Se realizó, en condiciones de ayuno, una pH-metría gástrica de 6 horas en dos períodos: basal (1 hora antes del medicamento) y post-droga (5 horas) luego de la administración oral de una dosis única de ranitidina (75 mg) + 5 g de antiácidos efervescentes (bicarbonato sódico, ácido cítrico, carbonato sódico). Resultados: dado que dos pacientes no completaron el estudio de pH por razones técnicas, se analizaron los resultados de 18 voluntarios. El pH intragástrico basal fue de 1.33±0.12 (promedio ± DS) y se elevó a 5.1±0.3 como promedio de todo el período post-droga (p<0.00001). El incremento de pH fue inmediato; así los valores de pH=3 y pH=4 fueron alcanzados en 27 seg, rango: 0-189 y 54 seg, rango 27- 3.600, respectivamente (mediana, rango). El pH se mantuvo inicialmente por encima de 4 durante 23.0±5 minutos. El tiempo con pH < 4 durante las 5 horas post-droga fue de 96± 17 minutos (32% del tiempo total). Conclusión: nuestro estudio confirma el efecto rápido y persistente determinado por la combinación de sales antiácidas y bajas dosis de ranitidina. De este modo esta asociación podría ser efectiva, rápida y segura frente a pirosis esporádica o síntomas de reflujo gastro-esofágico leve.