AIM:To review and summarize drug metabolism and its related interactions in prescribing drugs within the similar therapeutic or structural class for gastrointestinal disease treatment so as to promote rational use of ...AIM:To review and summarize drug metabolism and its related interactions in prescribing drugs within the similar therapeutic or structural class for gastrointestinal disease treatment so as to promote rational use of medicines in clinical practice.METHODS:Relevant literature was identified by performing MEDLINE/Pubmed searches covering the period from 1988 to 2006.RESULTS:Seven classes of drugs were chosen,including gastric proton pump inhibitors,histamine H2-receptor antagonists,benzamide-type gastroprokinetic agents,selective 5-HT3 receptor antagonists,fluoroquinolones,macrolide antibiotics and azole antifungals.They showed significant differences in metabolic profile(i.e.,the fraction of drug metabolized by cytochrome P450(CYP),CYP reaction phenotype,impact of CYP genotype on interindividual pharmacokinetics variability and CYP-mediated drug-drug interaction potential).Many events of severe adverse drug reactions and treatment failures were closely related to the ignorance of the above issues.CONCLUSION:Clinicians should acquaint themselves with what kind of drug has less interpatient variability in clearance and whether to perform CYP genotyping prior to initiation of therapy.The relevant CYP knowledgehelps clinicians to enhance the management of patients with gastrointestinal disease who may require treatment with polytherapeutic regimens.展开更多
AIM： To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use.METHODS： Using a structured pro forma, we conducted a two-month survey of the electronic pre...AIM： To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use.METHODS： Using a structured pro forma, we conducted a two-month survey of the electronic prescriptions containing immediate-release （IR） or sustained-release （SR） product of clarithromycin for outpatients with gastrointestinal diseases in a 2200-bed general hospital. Suitability of the prescription was audited retrospectively. RESULTS： One hundred and sixty-four prescriptions of SR product and 110 prescriptions of IR product were prescribed for gastrointestinal disease treatment. Among prescriptions for anti-Helicobacter pylori （H pylori） therapy, triple therapy take the dominant position （91.8%）, followed by quadruple therapy （4.3%） and dual therapy （3.9%）. Amoxicillin was the most frequently co-prescribed antibiotic.Furazolidone and levofloxacin are used more widely than metronidazole or tinidazole. Clarithromycin SR was administered at inappropriate time points in all prescriptions. Fifty percent of all prescriptions of clarithromycin SR, and 6.4% of prescriptions of clarithromycin IR, were prescribed at inappropriate dosing intervals. Surprisingly, disconcordance between diagnoses and indications was observed in all prescriptions of clarithromycin SR which has not been approved for treating Hpy/ori infection although off-label use for this purpose was reported in literature. On the contrary, only one prescription （0.9%） of clarithromycin IR was prescribed for unapproved indication （i.e. gastro-oesophageal reflux disease）. 1.4% of prescriptions for chronic gastritis or peptic ulcer treatment were irrational in that clarithromycin was not co-prescribed with gastric acid inhibitors. Clinical significant CYP3A based drug interactions with clarithromycin were identified. CONCLUSION： There is a great scope to improve the quality of clarithromycin prescribing in patients with gastrointestinal disease, especially with regard to administration schedule, concordance between indications and diagnoses and management of drug interactions.展开更多
Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers...Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.展开更多
基金the Scientific Research Project of Zhejiang Provincial Bureau of Education,No. 20061449,No. 20010535
文摘AIM:To review and summarize drug metabolism and its related interactions in prescribing drugs within the similar therapeutic or structural class for gastrointestinal disease treatment so as to promote rational use of medicines in clinical practice.METHODS:Relevant literature was identified by performing MEDLINE/Pubmed searches covering the period from 1988 to 2006.RESULTS:Seven classes of drugs were chosen,including gastric proton pump inhibitors,histamine H2-receptor antagonists,benzamide-type gastroprokinetic agents,selective 5-HT3 receptor antagonists,fluoroquinolones,macrolide antibiotics and azole antifungals.They showed significant differences in metabolic profile(i.e.,the fraction of drug metabolized by cytochrome P450(CYP),CYP reaction phenotype,impact of CYP genotype on interindividual pharmacokinetics variability and CYP-mediated drug-drug interaction potential).Many events of severe adverse drug reactions and treatment failures were closely related to the ignorance of the above issues.CONCLUSION:Clinicians should acquaint themselves with what kind of drug has less interpatient variability in clearance and whether to perform CYP genotyping prior to initiation of therapy.The relevant CYP knowledgehelps clinicians to enhance the management of patients with gastrointestinal disease who may require treatment with polytherapeutic regimens.
基金Zhejiang Provincial Bureau of Education,No.20070227Zhejiang Medical Association,No.2007ZYC18Association of Zhejiang Hospital Administration,No.2007AZHA-KEB312
文摘AIM： To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use.METHODS： Using a structured pro forma, we conducted a two-month survey of the electronic prescriptions containing immediate-release （IR） or sustained-release （SR） product of clarithromycin for outpatients with gastrointestinal diseases in a 2200-bed general hospital. Suitability of the prescription was audited retrospectively. RESULTS： One hundred and sixty-four prescriptions of SR product and 110 prescriptions of IR product were prescribed for gastrointestinal disease treatment. Among prescriptions for anti-Helicobacter pylori （H pylori） therapy, triple therapy take the dominant position （91.8%）, followed by quadruple therapy （4.3%） and dual therapy （3.9%）. Amoxicillin was the most frequently co-prescribed antibiotic.Furazolidone and levofloxacin are used more widely than metronidazole or tinidazole. Clarithromycin SR was administered at inappropriate time points in all prescriptions. Fifty percent of all prescriptions of clarithromycin SR, and 6.4% of prescriptions of clarithromycin IR, were prescribed at inappropriate dosing intervals. Surprisingly, disconcordance between diagnoses and indications was observed in all prescriptions of clarithromycin SR which has not been approved for treating Hpy/ori infection although off-label use for this purpose was reported in literature. On the contrary, only one prescription （0.9%） of clarithromycin IR was prescribed for unapproved indication （i.e. gastro-oesophageal reflux disease）. 1.4% of prescriptions for chronic gastritis or peptic ulcer treatment were irrational in that clarithromycin was not co-prescribed with gastric acid inhibitors. Clinical significant CYP3A based drug interactions with clarithromycin were identified. CONCLUSION： There is a great scope to improve the quality of clarithromycin prescribing in patients with gastrointestinal disease, especially with regard to administration schedule, concordance between indications and diagnoses and management of drug interactions.
基金Supported by Zhejiang Provincial Bureau of Education, No. 20070227Zhejiang Medical Association, No.2007ZYC18Association of Zhejiang Hospital Administration, No. 2007AZHA-KEB312
文摘Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R(+)-rabeprazole] (10 mg) was found to be more effective than rabeprazole (20 mg) in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors (PPIs). A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships (QSARs) are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.
