Absorption Of Ranitidine Research Articles

Effect of domperidone on cimetidine and ranitidine absorption in rabbits.

Cimetidine and ranitidine absorption were studied after oral administration to rabbits, alone or in combination with oral and intravenous domperidone. Blood samples were collected before and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.5, and 6.0 h after cimetidine and ranitidine administration. Assays of cimetidine and ranitidine in plasma samples were carried out using HPLC method. Domperidone overall significantly reduced the area under the plasma concentration-time curve (AUC) by approximately 30 per cent for both drugs. However, domperidone had little effect on the maximum plasma concentration (Cmax), the time taken to reach the maximum plasma concentration (Tmax), and the elimination half-life (t1/2) of cimetidine and ranitidine. The results suggest that domperidone affects the extent but not the rate of cimetidine and ranitidine absorption by enhancing gastric emptying.

Lack of Clinically Significant In Vitro and In Vivo Interactions between Ranitidine and Sucralfate

The hypothesis that the cytoprotective agent sucralfate (sucrose octakis(hydrogen sulfate)-aluminum complex) interacts with the H2-antagonist ranitidine (N-[2-[[5-[(dimethylamino)methyl]furfuryl]-thio]ethyl]-N'-methyl-2-nitro-1, 1-ethenediamine) by decreasing ranitidine absorption was tested in vitro and in vivo. The in vitro results show that ranitidine may bind to a small extent (∼10%) to sucralfate paste in the gastrointestinal fluids. The in vivo interaction of 150mg of ranitidine and 1g of sucralfate was evaluated in a crossover study in six healthy volunteers. The results indicate no significant difference in pharmacokinetic parameters when ranitidine was given alone and in combination with sucralfate. Thus, ranitidine bioavailability is not diminished by sucralfate and the two drugs can be given concomitantly. For the determination of bioavailability, it has to be taken into account that renal clearance of ranitidine is lower after oral than after intravenous administration, and that enterohepatic recirculation of the drug is likely.

Oral Ranitidine in Labour

Ranitidine 150 mg orally was given every 6 hours to 909 women in labour, while a control group of 378 women received conventional alkali therapy. No differences in incidences of operative intervention, placental retention or post-partum haemorrhage were observed between groups. Gastric sampling during emergency anaesthesia revealed a pH less than 2.5 in four of 51 women who received ranitidine and in two of 31 women who received magnesium trisilicate. Gastric volumes were slightly lower (mean 83 ml) in the study group than in the control group (mean 122 ml). Absorption of ranitidine was greatly slowed following narcotic administration and gastric volume was significantly higher in those patients given narcotics in labour. Apgar scores were similar in both groups of infants, and babies whose mothers were given ranitidine showed no delay in achieving high gastric acidity and no increase in bacterial colonization of the gastro-intestinal tract. Low levels only of ranitidine were found in the blood of babies at 2-3 hours and approximately 12 hours after birth.

The effects of antacid and propantheline on the absorption of oral ranitidine.

The effects of propantheline bromide and an aluminum hydroxide/magnesium hydroxide suspension on absorption of ranitidine were evaluated in 12 healthy volunteers according to a Latin square design. Ranitidine 150 mg was administered alone, with 30 ml antacid or preceded by 15 mg propantheline. Ten serum samples were obtained over 12 hours during each treatment period for measurement of ranitidine concentration. The antacid had no significant effect on ranitidine absorption, but propantheline increased the relative bioavailability of ranitidine by 22%. In addition, there was a trend, although not statistically significant, for propantheline to increase the maximum ranitidine serum concentration and the time to maximum serum concentration. Ranitidine can be administered concomitantly with the evaluated doses of antacid and propantheline without a clinically significant alteration in its absorption.

Clinical pharmacokinetics of ranitidine.

The methods available for assaying ranitidine in plasma and both the drug and its metabolites in urine are high-performance liquid chromatography and radioimmunoassay. Following oral administration, the absorption of ranitidine in normal individuals has been found to be rapid, with peak plasma concentrations occurring at 1 to 3 hours. Peak plasma concentrations bear a constant relationship to dose, but vary widely between individuals. The bioavailability of ranitidine after oral administration is approximately 50% due to presystemic hepatic metabolism. Plasma protein binding of ranitidine is approximately 15% and the apparent volume of distribution is greater than body volume. Ranitidine penetrates very poorly into the cerebrospinal fluid but is concentrated into breast milk. After intravenous administration, plasma concentrations decay in a biexponential manner. The elimination half-life is almost 2 hours and is somewhat longer after oral administration. Plasma clearance is approximately 600 ml/min of which most is renal clearance. Elimination of ranitidine is not dose-dependent. Hepatic metabolism is the other major route of elimination and there may be some enterohepatic recycling of the drug. Food has no effect on the kinetics of ranitidine but concurrent administration of antacids reduces its absorption. Renal disease causes an increase in ranitidine plasma concentrations through reduced clearance and possibly increased bioavailability. Chronic liver and some reduction in clearance. In the elderly, there is a reduction in clearance and prolongation of the elimination half-life but little effect on bioavailability. There is a relationship between plasma concentrations of ranitidine and suppression of gastric acid production but wide interindividual variability.