The Infuence Of Acid-inhibitory Drugs On Bismuth Absorbtion In Rats

BackgroundBismuth compouds are common drugs in China,which have been used for more than 200 years for the treatment of skin lesions,syphilis,and various gastrointestinal disorders.From a gastroenterology perspective, these drugs have been used as mucosal protective agents to treat peptic ulcer disease, dyspepsia,etc.The eruption of bismuth encephalopathy in the 1970s led to the reduction of bismuth compouds use.Since bismuth compouds were found to inhibit the growth of Helicobacter pylori(Hp) in the 1980s,led to a renewed interest in bismuth compounds.The Maastricht-IVconsensus recomenned the bismuth contained quadruple therapy as the fist-line therapy in the regions with high clarithromycin resistance rate.According to the consensus,the bismuth contained quadruple therapy has been widely used in our nation.The currently common use of bismuth compounds are colloidal bismuth subcitrate(CBS)and Colloidal Bismuth Pectin(CBP),however,each version of pharmacopeia after the founding of the state indicated that acid-inhibitory drugs can not use in combination with bismuth compouds.The acid-inhibitory drugs can increase the absorbtion of the bismuth, which may lead to the result of bismuth encephalopathy, but the quadruple therapy contains acid-inhibitory drugs and bismuth compounds.Moreover,some studies showed that high-dose proton pump inhibitors in the eradication of Hp can increase the cure rate. In addition,the phenomenon of using bismuth as mucosal protective agents and combining with antasids is not uncommon.According to the previous studies,the acid-inhibitory drugs can increase the absorbtion of the bismuth,and long-term of high plasma bismuth may cause extrapyramidal injury and renal failure,therefore,attention should be paied to the potential risks caused by the accumulation of bismuth.There are a variety of bismuth compouds at present,the effect of diferent kinds and diferent dose of acid-inhibitory drugs on bismuth absorbtion is still unknown.Therefore,we designed a randomized controlled animal studies.Objective1.To explore the influence of diferent kinds of acid-inhibitory drugs on bismuth absorbtion.2.To explore the influence of diferent dose of acid-inhibitory drug on bismuth absorbtion.Methods36 male Wistar rats were divided into 6 groups randomly. There were 6 rats in each group,named group A to E.Group A(control group) were adminstrated with distilled water, group B were adminstrated with a dosage of bismuth at 40 mg/kg, group C were adminstrated with a dosage of bismuth at 40 mg/kg and famotidine at 3.6 mg/kg, group D were adminstrated with a dosage of bismuth at 40 mg/kg and esomeprazole at 3.6mg/kg,group E were adminstrated with a dosage of bismuth at 40 mg/kg and rabeprazole at 1.8mg/kg,group F were adminstrated with a dosage of bismuth at 40 mg/kg and rabeprazole at 3.6mg/kg0 All the rats in each groups were adminstrated once daily, lasting for 14 days.The serum and nephritic bismuth concentration of all the rats in each group were observed after 14 days.ResultThere was a significant difference between control group and group bismuth-alone(P=0.002),bismuth+famotidin(P=0.001),bismuth+esomeprazole(P=0.003) for serum bismuth concentration.Significant differences were also found between bismuth-alone and bismuth+famotidin(P=0.032),bismuth+esomeprazole(P=0.040) for serum bismuth concentration.There was no difference between other groups.The ratio of serum bismuth concentration above 50 ng/ml of each group were 0/6 (cntrol group),0/6 (bismuth-alone),6/6 (bismuth+famotidine),6/6 (bismuth+esomeprazole), 6/6 (bismuth+rabeprazole standard dose),5/6 (bismuth+rabeprazole double-dose).The ratio of serum bismuth concentration above 100 ng/ml of each group were 0/6 (cntrol group),0/6 (bismuth-alone),4/6 (bismuth+famotidine),5/6 (bismuth+esomeprazole), 5/6 (bismuth+rabeprazole standard dose),4/6 (bismuth+rabeprazole double-dose). There was a significant difference between control group and other groups for nephric bismuth concentration(compared with group bismuth-alone,P=0.002; bismuth+ famotidin,P=0.001; bismuth+esorneprazole,P=0.003; bismuth+rabeprazole standard dose,P=0.004; bismuth+rabeprazole double-dose,P<0.001).Conclusionl.Famotidin and esomeprazole can significantly increase the absorbtion of bismuth,while both rabeprazole standard dose and double dose did not significantly increase the absorbtion of bismuth in the present study.The possible reason was that rabeprazole interacted with bismuth in rats due to its special molecular structure,which reduced the absorbtion of bismuth.The present stdudy suggested that rabeprazole may improve the safety of bismuth in the qurdruple therapy for Hp eradication,which remains to be elucidated by further studies.Combination of acid-inhibitory drugs and bismuth compounds increased the risk of dangerous level of serum bismuth, which should be avoid to use for long-term.2.The application of bismuth could lead to the accumulication in the kedney,which should be avoid to use for long-term in clinical practice. Acid-inhibitory drugs were not observed to increase the accumulication in two weeks combination with bismuth in this study.