| [Background and Objective] Gastrointestinal bleeding remains frequent emergency in children and the most common causes include peptic ulcer disease , erosive gastritis , duodentitis, reflux oesophagitis, oesophague varicosity burst. Antisecretory therapy has been expected to be an important means for the treatment of gastrointestinal bleeding. The proton-pump inhibitors (PPIs) are the most effective in acid suppression and the H2RAs generally are ineffective at reaching improved prognosis in pediatric patients with gastrointestinal bleeding. Famotidine as a carbamidine thiazole derivative is reversible competitive histamine H2-receptor antagonis that recent year has an approved, labeled indication for the treatment of peptic ulcer disease and gastrointestinal bleeding conditions in adults, but less experience has been available with the pharmacokinetics and pharmacodynamics of intravenous famotidine in pediatric populations and no report of famotidine has been published in Chinese children. The appropriate dosing requirements are not known for pediatric patients. The purpose of this study was to analyze clinical efficacy , safety and acid suppression of intravenous administration famotidine with observing hemostatic effect and adverse effect and monitoring the intragastric acidity in gastrointestinal bleeding children, and to further assess the optimum dose and dosing interval for sick children using solid phase preparatorychromatography to extract famotidine from plasma sample and a high-performance liquid chromatography (HPLC) to quantitate famotidine plasma concentration. [Methods] 105 patients hospitalized of gastrointestinal bleeding were enrolled into the study (boy 79 and girl 26, ranging from 3 month to 15 year age). All of the patients has not undergone antacid therapy within 4 weeks and has normal renal and hepatic function. Patients were randomly divided into three groups and were administrated intravenously twice daily with an internal of a week of famotidine 0.9 mg/kg (famotidine therapy group A, 39 patients), 0.5 mg/kg (famotidine therapy groupB, 35 patients), and omeprazole 0.9 mg/kg (omeprazole control group, 31 patients) respectively. The hemostatic effect and adverse effect were requested to be observed for all three groups and blood and urine routine and renal and hepatic function were also detected. Twenty-four-hour intragastric pH was monitored to observe changes of intragastric acidity before and after famotidine dosing in famotidine therapy groupA (4 patients) and famotidine therapy group B (3 patients). Analysis was performed by using SPSS program (version 10.0), P values of < 0.05 was considered statistically significant. From therapy group, after baseline blood sample (1ml) was obtained, intravenous dose of famotidine 0.9mg/kg (group A, 15 patients) and 0.5mg/kg (group B, 8 patients) were administered Via a Syringe pump within an hour and serial blood samples (1ml each) were collected 0.5 , 1, 2, 4 and 12 hours after completion of the famotidine administration. After collection, blood samples were centrifuged and extracted famotidine by solid phase preparatory chromatography with an Oasis cartridge and famotidine plasma concentration was quantitated by a high-performance liquid chromatography (HPLC). Pharmacokinetic parameters of famotidine the elimination half-life [tt/2(e)] , steady state volume of distribution (V), the total plasma clearance (Cl) were calculated.[Results] 1 , The hemostatic effectual rate at 24 houn 24-72 hour and the global effective rate after famotidine 0.9mg/kg and 0.5mg/kg intravenous administration were58.97%, 35.90%, 94.87% and 42.86%> 34.29%, 77.14%, respectively. The former were no significant difference to those in control group, but the latter were significantly lower than those in the therapy group A and the control group, indicating that Chinese famotidine 0.9mg/kg intravenous was equal with omeprazole, superior to famotidine 0.5mg/kg. 2, Mean intragastric pH was 2.15 and 1.97 respectively before the intravenous infusion of famotid...
|
PDF Full Text Request