International journal of clinical pharmacology and biopharmacy最新文献

{"title":"[The propagation of aminoglycoside transferases in gram negative bacteria].","authors":"B Wiedemann,&nbsp;G Tetzlaff,&nbsp;U van Treeck","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Molecular genetic and enzymatic studies on Gram-negative bacteria from hospital specimens give the following picture on surveillance of aminoglycoside transferases: The most frequent enzymes inactivate streptomycin only, AAD- (3'') and APH-(3''). Only 15% of the isolated enzymes inactivate gentamycin, tobramycin, sisomycin or amikacin. The most frequent of these are AAD-(2'') with 7% and AAC-(6') IV with 3%, both enzymes inactivate a wide range of substrates. The high frequency of streptomycin inactivating enzymes is due to the high incidence of linked resistance markers. A plasmid rPB1 is described, that is present in about 10% of all clinical isolates of E. coli. It has a molecular weight of 4. 1 Mdal and typical restriction pattern.</p>","PeriodicalId":75937,"journal":{"name":"International journal of clinical pharmacology and biopharmacy","volume":"17 3","pages":"138-44"},"PeriodicalIF":0.0,"publicationDate":"1979-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11635502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-pass effect of coumarin in man.","authors":"W A Ritschel,&nbsp;M E Brady,&nbsp;H S Tan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Blood level versus time data upon i.v. and p.o. administration of coumarin in a cross-over study have been analyzed for extent of bioavailability (EBA) and first-pass effect (FPE). In whole blood the parent drug, coumarin (C), and its main metabolite, 7-hydroxycoumarin (7HC), after hydrolysis of the glucuronide were determined. Comparison of the areas under the curve (AUCO leads to infinity) for C and 7HC upon i.v. and p.o. administration revealed that all of the drug is absorbed; however, only approximately 2-6% of C reaches systemic circulation in intact form. Hence, extensive first-pass effect must be assumed. The fraction of unchanged drug reaching systemic circulation predicted from the i.v. study fFPE varied between 0 and 38% assuming a liver blood flow rate (LBF) of 1.53 1/min. When corrected for individual LBF the fPFE varied between 2.5 and 13%. The question whether the FPE is only due to metabolism in the liver or in part due to biotransformation in the intestinal lumen, gut wall and/or portal blood will be the subject of a further paper. It is suspected that C is the pro-drug and 7HC the pharmacologic active moiety.</p>","PeriodicalId":75937,"journal":{"name":"International journal of clinical pharmacology and biopharmacy","volume":"17 3","pages":"99-103"},"PeriodicalIF":0.0,"publicationDate":"1979-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11635503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Production of endogenous D-glucaric acid and oxidative N-demethylation of amidopyrine in man: lack of correlation.","authors":"K J Freundt","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In adult male subjects there was no positive correlation between the 24-hr urinary excretion of D-glucaric acid (D-GA) and the metabolic formation of 4-aminoantipyrine (AAP) from amidopyrine. It is concluded that in man the urinary D-GA excretion rate cannot be regarded in general as an indirect measure of the activity of microsomal drug conversion by means of mixed-function oxidases (MFO). Normal urinary value for D-GA: 16.3 +/- 1.5 (mean +/- SEM) mumols saccharo-1,4-lactone/24 hr as equivalent.</p>","PeriodicalId":75937,"journal":{"name":"International journal of clinical pharmacology and biopharmacy","volume":"17 3","pages":"104-6"},"PeriodicalIF":0.0,"publicationDate":"1979-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11633599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aminoglycoside-modifying enzymes.","authors":"J Davies","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75937,"journal":{"name":"International journal of clinical pharmacology and biopharmacy","volume":"17 3","pages":"137"},"PeriodicalIF":0.0,"publicationDate":"1979-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11633602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical-pharmacological aspects, application and effectiveness of total parenteral nutrition in surgical patients.","authors":"R Dionigi,&nbsp;R Guaglio,&nbsp;A Bonera,&nbsp;M Cerri,&nbsp;R Rondanelli,&nbsp;M Campani","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The term \"total parenteral nutrition\" (TPN) refers to the maintenance of an adequate nutritional status, normal body weight and positive nitrogen balance solely by intravenous means. It requires solutions providing calories, amino acids and other nutrients in amounts much greater than those indicated for maintenance of normal body weight. Nutrient solutions have been studied, selected and prepared in our Hospital Pharmacological Service utilizing a sterile closed system, which allows large-volume filtering, sterilizing and bottling devices. For maintenance of weight gain in adults, a basic formula is employed, which provides 1,100 Kcal/1 with pure crystalline amino acids mixed with 50% anhydrous dextrose in water in a ratio of 5.8:1 (160 Kcal:1 g nitrogen). Minerals and vitamins are added to the base solution prior to use and may be increased or decreased by simple addition or omission depending on the patient's condition. This paper is based on 192 surgical patients who received TPN and have been followed in strict cooperation between the Hospital Pharmacological Service and the Surgical Department. The patients, ranging from 23 to 79 years of age, with life threatening diseases and unable to maintain adequate nutrition by the oral route, received TPN through a central catheter inserted via subclavian puncture (146 cases) or through a surgically created internal A-V fistula (46 cases). The condition of the patients generally improved within a few days after starting TPN; and weight gain, wound healing, general improvement and a shorter period of hospitalization were observed. TPN could be efficiently combined with oncologic treatment, and a significant improvement of the patients' performance status and decrease of toxic side-effects due to chemotherapeutic agents were observed. TPN has been successfully applied also in patients with fistulas of the alimentary tract obtaining spontaneous closure and in patients with ulcerative colitis, showing its beneficial effect in allowing complete bowel rest for healing. No major complications or deaths could be attributed to TPN or to the route of administration.</p>","PeriodicalId":75937,"journal":{"name":"International journal of clinical pharmacology and biopharmacy","volume":"17 3","pages":"107-18"},"PeriodicalIF":0.0,"publicationDate":"1979-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11327207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Penetration through the gram-negative cell wall: a co-determinant of the efficacy of beta-lactam antibiotics.","authors":"W Zimmermann","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Resistance of gram-negative bacteria to beta-lactam antibiotics is based mainly on two mechanisms: hydrolysis by beta-lactamases and exclusion of the antibiotics from their target sites in the inner membrane. This article describes the use of Pseudomonas aeruginosa K 799/WT and a mutant of this strain (K 799/61) to assess the role of the outer membrane as a permeability barrier to penicillins and cephalosporins. The data confirm the importance of good penetration for a beta-lactam to be active against Pseudomonas. The second part illustrates the interplay of beta-lactamases and the outer membrane in the resistance of Escherichia coli to beta-lactams. A method to determine membrane permeability parameters parameters is given. The results support the idea that only a combined consideration of inactivating enzymes and penetration barriers can lead to a better understanding of the efficiency of the defence mechanisms which gram-negative bacteria can invoke against beta-lactam antibiotics.</p>","PeriodicalId":75937,"journal":{"name":"International journal of clinical pharmacology and biopharmacy","volume":"17 3","pages":"131-4"},"PeriodicalIF":0.0,"publicationDate":"1979-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11327208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacodynamic and spirometric responses to a sustained-release theophylline capsule.","authors":"C J Falliers","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A prolonged therapeutic effect following a single oral dose of theophylline and maintenance of an adequate therapeutic blood level of theophylline is an important factor in the management of chronic bronchial asthma. Eighteen adult asthmatics, nine of whom were females and nine males, aged between 21-53 years, were given a sustained release theophylline capsule, 250 mg, every 12 hours and pulmonary mechanical functions as well as serum theophylline levels were studied. All patients received Elixophyllin Elixir, 250 mg, and their serum level as well as pulmonary functions were studied and compared to those after receiving the sustained release capsules. In these patients, after isoproterenol inhalation, an average of 25.6% improvement in FEV1 was observed while after placebo there were very minimum changes. At the steady-state of sustained release theophylline capsule administration, an average of 20% improvement of FEV1 was observed at the five hour period and sufficient bronchodilation expressed as FEV1 was observed for a 10-12 hour period. Indeed, a sustained release theophylline capsule fulfilled the requirement that it adequately maintained therapeutic theophylline level of the blood and improved bronchodilation lasting up to 12 hours.</p>","PeriodicalId":75937,"journal":{"name":"International journal of clinical pharmacology and biopharmacy","volume":"17 3","pages":"125-30"},"PeriodicalIF":0.0,"publicationDate":"1979-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11633601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydralazine therapy and acetylator phenotype.","authors":"E Iisalo,&nbsp;T Laine,&nbsp;A Lehtonen,&nbsp;R Sellman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The acetylator phenotype was studied in 21 hypertensive patients receiving chronic treatment with dihydralazine and other antihypertensive drugs. Plasma dihydralazine concentrations were measured 6 hours after the morning dose of the drug. There were no significant differences between the slow and fast acetylators 1) in the daily dose of dihydralazine needed, 2) in the concentrations of dihydralazine achieved in plasma, 3) in the dose/concentration-relationship of dihydralazine or 4) in the appearance of side effects. Antinuclear antibodies were found in five patients. Four of them were fast acetylators. The lowest dose/concentration relationship was found in a patient with impaired renal function. According to these results the acetylator phenotype seems to be an unimportant factor in therapy with dihydralazine. More investigation will be needed in order to elucidate the metabolism of dihydralazine.</p>","PeriodicalId":75937,"journal":{"name":"International journal of clinical pharmacology and biopharmacy","volume":"17 3","pages":"119-24"},"PeriodicalIF":0.0,"publicationDate":"1979-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11633600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta-lactamases.","authors":"M H Richmond","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75937,"journal":{"name":"International journal of clinical pharmacology and biopharmacy","volume":"17 3","pages":"135-6"},"PeriodicalIF":0.0,"publicationDate":"1979-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11525605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myelofibrosis--pathophysiology and treatment.","authors":"D R Cole,&nbsp;J Pung,&nbsp;F Pung,&nbsp;D F Cole","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A case of myelofibrosis successfully treated by the use of splenectomy has been reported. The feeling of the authors is that splenectomy should be considered at a much earlier stage of the disease, when the patient is a better risk with a longer survival. We see no valid physiological reasoning for leaving a spleen in, which is valueless to the patient in addition to causing multiple side effects, directly and indirectly from its size and overactivity. This is especially true when attempts to reduce the size have potential hazards, none are completely effective and when the physiological necessity for this reticulo endothelial site seems to be unnecessary. Perhaps it would be of greatest value if all cases of myelofibrosis should be seen at the inception and throughout by the hematological and surgical service together.</p>","PeriodicalId":75937,"journal":{"name":"International journal of clinical pharmacology and biopharmacy","volume":"17 2","pages":"68-70"},"PeriodicalIF":0.0,"publicationDate":"1979-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11579236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}