Infusion Of Famotidine Research Articles

Comparison of the efficacy of esomeprazole and famotidine against stress ulcers in a neurosurgical intensive care unit

SummaryBackgroundTo compare the efficacy of esomeprazole and famotidine against stress ulcers and the association of these prophylactic agents with ventilator‐associated pneumonia in patients admitted to neurosurgical intensive care unit (ICU).Patients and MethodsSixty patients were randomly allocated into two groups (the esomeprazole and famotidine groups; n = 30 each) to receive prophylaxis medication for 7 days within 24 hours of admission in a neurosurgical ICU. Patients in the esomeprazole group received esomeprazole (40 mg) dissolved in water once a day through a nasogastric tube, whereas patients in the famotidine group received an intravenous infusion of famotidine (20 mg) every 12 hours. We then compared the occurrence of overt upper gastrointestinal bleeding and ventilator‐associated pneumonia between these two groups.ResultsOne patient in the famotidine group had overt upper gastrointestinal bleeding (3.3%), whereas the bleeding was not observed in patients in the esomeprazole group. Ventilator‐associated pneumonia occurred in one patient (3.3%) from each group. One patient died within 30 days (3.3%) in the esomeprazole group and three patients (10%) died in the famotidine group. There was no difference in the occurrence of overt upper gastrointestinal bleeding (p = 1.000), ventilator‐associated pneumonia (p = 1.000), and 30‐day mortality (p = 0.612) between these two groups.ConclusionIn this small‐scale study, the effect of administration of esomeprazole through a nasogastric tube on stress ulcer was similar to that of intravenous famotidine infusion in neurosurgical ICU patients. In addition, the association between prevalence of ventilator‐associated pneumonia and administration of esomeprazole was also similar to that observed with famotidine infusion.

The clinical efficacy of pantoprazole for bleeding peptic ulcers associated with NSAIDs in elderly patients

Objective To observe the clinical efficacy of pantoprazole in the treatnent of NSAIDs-related bleeding peptic ulcers in elderly patients.Methods 100 elderly patients with NSAIDs-related bleeding peptic ulcers were randomly selected and then divided into study group and control group.The control group received intravenous infusions of famotidine,and the study group received intravenous infusions of pantoprazole.The effect of hemostasis,re-bleeding,and adverse reactions were compared between the two groups.Results After a course of treatment,the total effectiveness rate for hemostasis was 94％ in the study group and 82％ in the control group,with a statistical difference (P＜0.05).The rate of re-bleeding rate was significantly lower in the study group than in the control group (6％ vs.22％,P＜0.05).Conclusions Pantoprazole is safe and effective in the treatment of elderly patients with NSAIDs-related bleeding peptic ulcer. Key words: Bleeding peptic ulcer; NSAIDs; Pantoprazole

T1080 Effects of Rabeprazole Sodium and Ranitidine Hydrochloride On Gastric Acidity for 2 Consecutive Weeks: A Randomized, Open-Label, Two-Way Crossover Study in Healthy Subjects Using BRAVO ® Capsules Fixed to the Stomach

inhibition in the early post-administration phase (48 hours) in relative to CYP2C19 genotype status. Methods: Fifteen Helicobacter pylori-positive volunteers with three different CYP2C19 genotypes were dosed with twice-daily intravenous infusions of famotidine 20 mg alone, omeprazole 20 mg alone, omeprazole 10 mg plus famotidine 10 mg (half), and omeprazole 20 mg plus famotidine 20 mg (full) for 2 days. The subjects underwent 48-hour intragastric pH monitoring. Results: With homozygous extensive metabolizers (EMs) of CYP2C19, the median first 24-hour intragastric pH with full-concomitant regimen was 4.8 (range; 4.5 5.4), which was significantly higher than that with omeprazole alone [3.9 (2.6 4.7), p = 0.043] or famotidine alone [4.4 (3.8 4.9), p = 0.043]. In heterozygous EMs and poor metabolizers, the respective median first 24-hour pHs attained by omeprazole alone [5.8 (4.3 6.3) and 6.1 (5.3 7.4)] and full-concomitant [5.8 (5.1 6.4) and 5.8 (5.4 6.2)] regimens were significantly higher than those with famotidine alone [4.1 (3.9 6.5) and 4.7 (3.7 5.7), p = all 0.043]. Conclusions: The CYP2C19 genotyping test appears to be a useful tool for determining the optimal treatment for the prevention of hemorrhage or rebleeding from peptic ulcers. If the CYP2C19 genotype status is determined before the hemorrhage, an optimal intravenous infusion regimen consisting of a PPI and an H2RA can be selected based on pharmacogenetic and pharmacogenomic status. We recommend the following intravenous infusion regimens for the faster and stronger acid inhibition: the infusion of omeprazole 20 mg alone twice-daily for PMs and heterozygous EMs, and the concomitant infusion of omeprazole 20 mg plus famotidine 20 mg twice-daily for homozygous EMs.

Effect of famotidine on recurrent bleeding after successful endoscopic treatment of bleeding peptic ulcer

We investigated the effect of acid suppression therapy on recurrent bleeding after successful endoscopic treatment of bleeding peptic ulcer. A total of 400 patients with bleeding peptic ulcer received either intravenous infusion of famotidine (40 mg/day) (n = 207, 163 males, 44 females, mean age 61.5 years) or drip infusion of omeprazole (40 mg/day; n = 193, 134 males, 59 females, mean age 59.8 years) after successful endoscopic treatment. The fasting duration, hospital stay, volume of transfused blood, incidence of rebleeding and mortality were compared between the two groups. The incidence of rebleeding did not differ significantly between the famotidine group (9%) and the omeprazole group (8%). The mean hospital stay was significantly shorter in the omeprazole group (18.4 days) than in the famotidine group (21.5 days, P = 0.009). However, there was no statistically significant difference in fasting duration, volume of transfused blood or mortality. Our findings indicate that intravenous infusion of famotidine after successful endoscopic treatment is equivalent to drip infusion of omeprazole for prevention of recurrent bleeding.

Effect of Famotidine After Endoscopic Treatment on Bleeding Peptic Ulcers

Background and Aim: Peptic ulcers are the most common cause of upper gastrointestinal bleeding. The aim of our study was to investigate the effect of acid suppressive therapy after endoscopic treatment on bleeding peptic ulcer diseases. Patients and Methods: The 398 patients with bleeding peptic ulcers were divided into two groups those receiving drip infusion of PPI (40 mg/day) (n=165, 116 men, 49 women, mean age 59.8 yrs) and those receiving infusion of famotidine (40 mg/day) (n=233, 188 men, 45 women, mean age 61.5 yrs) after initial endoscopic treatment.

Pharmacokinetics and Pharmacodynamics of Famotidine in Infants

The pharmacokinetics and pharmacodynamics of intravenous famotidine were evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic indication for the prophylactic treatment of stress ulceration. After a 0.5-mg/kg infusion of famotidine, timed serum (n = 6), urine (24-hour collection), and repeated measurements of gastric pH were obtained. The mean +/- standard deviation maximum plasma concentration (Cmax) was 640.66 +/- 250.66 ng/mL, the elimination half-life (t1/2 beta) was 10.51 +/- 5.43 hours, and the apparent volume of distribution at steady state (Vdss) was 0.82 +/- 0.29 L/kg. Plasma clearance (Cl) and renal clearance (ClR) were 0.132 +/- 0.061 L/hr/kg and 0.093 +/- 0.056 L/hr/kg, respectively. No significant correlations were found between t1/2 beta, Vdss, Cl, and ClR and age. Six of the nine infants who had intragastric pH monitoring maintained a gastric pH > 4 until the final 24-hour sampling point. In this study, the t1/2 beta of famotidine was prolonged and the Vdss, Cl, ClR were reduced compared with corresponding parameters in previously reported studies of children older than one year of age and adults.

Pharmacokinetics and pharmacodynamics of famotidine in children.

The pharmacokinetics and pharmacodynamics of intravenous famotidine were studied in 12 children (1.1-12.9 years of age; mean weight +/- standard deviation = 27.6 +/- 21.2 kg) who were given the drug for prophylactic management of stress ulceration. After a 0.5-mg/kg infusion of famotidine, timed blood (n = 10) and urine (n = 6) samples and repeated evaluations of intragastric pH (n = 13) were obtained from each subject. Pharmacokinetic parameters were determined from curve fitting of serum concentration data. The mean (+/- SD) maximum serum concentration (Cmax) was 527.6 +/- 281.2 ng/mL, the elimination half-life (t1/2) was 3.2 +/- 3.0 hours, and the apparent steady-state volume of distribution (Vdss) was 2.4 +/- 1.7 L/kg. Plasma clearance (Cl) and renal clearance (ClR) were 0.70 +/- 0.34 L/hr/kg and 0.43 +/- 0.24 L/hr/kg, respectively. Over 24 hours, 73.0 +/- 27.3% of the dose was excreted unchanged in the urine (Fel). Pharmacodynamic analysis of gastric pH data using the sigmoid Emax model predicted that 50% of the maximal effect of famotidine (EC50) occurs at a serum concentration of 26.0 +/- 13.2 ng/mL. Children who did not have an initial intragastric pH < or = 4 did not have a significant response in pH after receiving famotidine. Although Vdss and Cl were higher in these children than those seen in adults, statistically significant relationships between these parameters and age were not observed in the study population. The pharmacodynamics and pharmacokinetics of famotidine in children older than one year of age appear to be similar to those noted in adults.

Intravenous Bolus versus Continuous Infusion of Famotidine or Ranitidine on 24 H Intragastric Acidity in Fasting Healthy Volunteers

Infusions of H2-receptor antagonists may be clinically indicated to maintain intragastric pH above 4 to reduce acute gastric mucosal lesions or to treat patients with bleeding peptic ulcers. Eight fasting healthy volunteers were randomly assigned to receive ranitidine infusion alone (150 mg/day), ranitidine infusion plus 50 mg bolus injection of ranitidine (total of 200 mg/day), famotidine infusion alone (40 mg/day) or famotidine infusion plus 40 mg bolus injection of famotidine (total of 80 mg/day). Gastric fluid contents were aspirated for 24 h and collected as half-hourly samples in which pH measurements were made. Measures analyzed were mean and median pH, percentage pH at or below 3, 4 or 5 for the 24 h period, daytime, evening and nighttime. The data for each of the variables were analyzed as a Latin square crossover design of variance therapy; base pH before treatment administration in each crossover phase was employed as the covariant. Significant differential treatment means were tested by Newman-Keul’s multiple range test at the 5% level of significance. The mean and median evening pH were higher after famotidine than after ranitidine infusion, but all other pH readings were similar when using these doses. The addition of an initial loading bolus of 50 mg ranitidine to the ranitidine infusion did not result in any added differences in pH, whereas the addition of an initial loading bolus of 40 mg famotidine to the famotidine infusion resulted in a higher 24 h median pH, as well as a lower percentage of pH values of 4 or below, 16.6% versus 28.5%, P&lt;0.05. However, the loading doses of ranitidine and famotidine were not equivalent in potency, and studies are needed to compare the potency of equivalent doses of ranitidine and famotidine when given by bolus plus infusion. Also the clinical relevance of these findings needs to be explored further in the type of individuals potentially requiring intravenous H2-receptor antagonists.

Bolus Infusion of Famotidine: Effects on Gastric pH by Repeated 12‐Hour Doses of 20 mg in Postoperative Patients

This study was carried out to assess the efficacy of intravenous (IV) famotidine in suppressing gastric secretion over a 48-hour period. Twenty postoperative patients requiring a nasogastric tube received famotidine 20 mg IV every 12 hours and gastric pH was measured continuously by means of an indwelling probe. A baseline recording was performed over the first 4 hours and then the drug was infused every 12 hours (q12h) over a 15-minute period for the subsequent 48 hours. The mean pH value achieved during each time segment under active treatment was significantly higher (P < .001) than the mean basal value. Also the density distributions of minutes spent at the various pH units confirm that famotidine is highly effective (P < .001) in raising and maintaining gastric pH above 4.0 units during most of the drug-related period (44 hours). It can be concluded that repeated intravenous boli of famotidine 20 mg every 12 hours allow us to obtain an effective control of intragastric acidity. The antisecretory action is consistent over the total 48-hour period examined and therefore the use of intermittent infusion of famotidine seems to be advisable, as opposed to the recommended continuous IV administration of cimetidine and ranitidine. There is, however, a considerable intersubject variability in the antisecretory response to the drug.

Hemodynamic Status during Famotidine Infusion

Histamine H2 antagonists, which reduce gastric acid secretion, are often used in the intensive care setting for the prophylaxis of stress ulcers. This double-blind, placebo-controlled study evaluated hemodynamic parameters in 11 stable, critically ill patients receiving famotidine. Repeated-measures ANOVA demonstrated that famotidine had no significant effect on baseline hemodynamic measurements and that there was no significant difference in hemodynamic values following the famotidine infusion as compared with NaCl 0.9% placebo (p greater than 0.05).

Use of automatic computerised pump to maintain constant intragastric pH.

We used continuous variable rate infusions of famotidine in eight normal volunteers under fasting conditions to raise intragastric pH to 5.0. An intragastric glass electrode continuously monitored acidity and this information was automatically computed to regulate an intravenous infusion system (GastroJet). The computer was programmed to aim for pH 6.0, increasing and lowering infusion rates accordingly. Two regimens were compared with placebo (10 mg bolus followed by infusion or infusion of famotidine alone). Volunteers were admitted to an investigation ward and each study was preceded by a standard normal meal. Hydration was maintained with intravenous fluids. During placebo treatment the median pH was 1.5 and the pH was less than 5.0 for 98% of the time. All volunteers responded to famotidine but dosage requirements varied (range 41 mg to 126 mg). The median pH rose to 6.5 when infusions of famotidine followed boluses and to 6.6 when infusions alone were used - the pH was less than 5.0 for 20% and 16% of the time respectively (p less than 0.05 Wilcoxon compared with placebo). Mean drug use was greater with boluses (98 mg v 87 mg p = 0.03: paired Student's t test) and onset was not apparently faster. Blood famotidine concentrations followed infusion rate changes. Famotidine infused by GastroJet maintains a high fasting intragastric pH and priming boluses are probably unnecessary.

Plasma famotidine concentration versus intragastric pH in patients with upper gastrointestinal bleeding and in healthy subjects

To study the concentration-response relationship of famotidine, we serially monitored intragastric pH and measured plasma drug concentrations simultaneously after an intravenous injection of this H2-receptor antagonist (0.1 mg/kg) in eight patients with upper gastrointestinal bleeding and in six healthy subjects. By applying the sigmoidal Emax model the mean (+/- SD) plasma famotidine concentrations associated with an intragastric pH of 4.0 in patients and healthy subjects were estimated to be 17.7 +/- 10.7 and 24.8 +/- 10.3 ng/ml, respectively (not significantly different). No significant differences were observed in the mean pharmacokinetic parameters between the two study groups. Multiple regression analysis revealed that not only a pharmacokinetic factor (i.e., elimination t1/2) but also a pharmacodynamic (or sensitivity) factor (i.e., a drug concentration associated with an intragastric pH of 4.0) contributed significantly (p less than 0.01) to the overall variability in the duration of antisecretory effect in our study subjects, with standardized partial regression coefficients of 0.54 and -0.63, respectively. Based on these data, we predict that around-the-clock control of a fasting intragastric pH above 4.0 can be attained by a continuous infusion of famotidine at rates ranging from 6 to 25 mg/day (mean +/- SD, 11 +/- 7 mg/day) in a 70 kg patient whose pharmacokinetic and pharmacodynamic characteristics are similar to those of our patients.