摘要:

PiZZ-deficient patients affected by a severe panlobular emphysema were treated with an infusion of industrial concentrates of purified &agr;1-antitrypsin (AAT). A treatment protocol was followed and the pharmacokinetic parameters were determined. The aim of this investigation was to consider the tissue distribution of AAT injected into untreated and treated patients, as well as into controls, in order to locate the labelled protein and map the kinetics of the protein deposit.Scintigraphies carried out on PiZZ patients and on controls confirmed a 3-pool pharmacokinetic model of AAT distribution. Three organs accounted for the predominant deposition of AAT: the liver, lungs and a very limited area of the upper digestive tract. At time 0, the distribution of the protein differed between controls and untreated patients. After 6 months of replacement therapy, the tissue distribution of AAT among treated and untreated PiZZ-deficient patients was not similar.The liver is one of the essential organs affected by the infusion of AAT. This study demonstrated that the digestive tissues are also affected by this replacement therapy. These observations should be useful in predicting tissue metabolism of the injected preparation, particularly when alternative routes of AAT administration are now possible.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

12 clinical studies on the use of roxithromycin 300mg daily in adult respiratory tract infection were subject to meta-analysis. Nine of the studies were comparative and 5 were from the published literature. Auditable individual patient data were reviewed for 11 of the 12 studies.4297 patients with respiratory tract infection were enrolled in these studies and 384 (8.9%) hadHaemophilus influenzaeidentified as a causative pathogen. Of these patients, 331 were treated with roxithromycin: 268 with 150mg twice daily and 63 with 300mg once daily. 53 patients were treated with comparator antibiotics. The primary analysis was undertaken on 300 cases whereH. influenzaewas the sole pathogen identified: 253 of these cases were treated with roxithromycin and 47 with comparator antibiotics.On a ‘per protocol’ (PPA) basis, the overall satisfactory clinical and bacteriological response for all roxithromycin regimens was 87% [95% confidence interval (CI), 82 to 92%] and 83%, respectively. Clinical response on an ‘intention-to-treat’ (ITT) basis was 80% (CI: 75 to 85%) excluding studies enrolling only hospitalised patients, and 78% (CI: 73 to 83%) for all cases. Clinical response (ITT) was marginally lower at 76% (CI: 72 to 82%) if mixed infections were included.Comparator antibiotics were amoxicillin/clavulanic acid, cefaclor, doxycycline, erythromycin and cotrimoxazole. A satisfactory clinical response (ITT) was obtained in 70% of cases treated with comparator antibiotics (CI: 57 to 83%). Roxithromycin demonstrated a response rate similar to that of amoxicillin/clavulanic acid and significantly better than erythromycin (p = 0.03). Although the numbers were small, roxithromycin was significantly more effective for the treatment of pneumonia in the directly comparative studies, with 93% success, compared with only 53% for the comparator antibiotics (p = 0.02). The response rate was similar to that reported for clarithromycin.Current minimum inhibitory concentration and disc zone susceptibility breakpoints of ≤ 1 mg/L and ≥ 22mm underestimate the clinical efficacy of roxithromycin againstH. influenzae.A disc zone diameter susceptibility breakpoint of ≥ 10mm is predictive of a successful outcome in 78% of cases (95% CI: 71 to 85%). This correlates well with recent recommendations to adopt susceptibility breakpoints of ≥ 10mm and ≤ 16 mg/L when using National Committee for Clinical Laboratory Standards (NCCLS) methodology.The results of this analysis support the empirical use of roxithromycin in respiratory tract infections whereH. influenzaeis a potential pathogen. Future clinical studies of respiratory tract infection with roxithromycin should evaluate these new breakpoints.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

With continuous arteriovenous haemodiafiltration (CAVHD), time-averaged clearance rates are higher than with intermittent haemodialysis. Indeed, drug removal rates may be high enough to warrant dose adjustment. In this study we measured the rate of drug clearance by CAVHD for 7 commonly used antibiotics: cefuroxime, cefotaxime, ceftazidime, imipenem, ciprofloxacin, tobramycin and vancomycin. By combining our data on clearance rates by CAVHD with literature data on drug distribution volumes and nonrenal clearance rates, we developed guidelines for drug dosage in intensive care patients treated by CAVHD. Dose adjustments during CAVHD treatment were deemed necessary for cefuroxime, ceftazidime, tobramycin and vancomycin.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The gastric tolerability of low dose conventional aspirin (acetylsalicylic acid) was compared with that of lysine acetylsalicylate in the dog. A total of 14 dogs were allocated to aspirin 250mg (n = 2) or 500mg (n = 4) tablets, lysine acetylsalicylate powder (LAS) corresponding to 250mg aspirin (n = 2) or to 500mg aspirin (n = 4), and to plain vehicle (n = 2). Animals were sacrificed after general anaesthesia. Macro- and microscopic examinations of gastric and duodenal mucosae were performed 3 or 5 hours after single dose oral administration. No significant duodenal lesions were found. On the gastric mucosa, vascular changes (oedema and microhaemorrhages) and foveolar atrophy were observed with a similar frequency and intensity in all groups receiving aspirin or LAS. Mucosal erosions with coagulative necrosis occurred only in the aspirin groups. Thus, the gastrotoxicity of aspirin at relatively low doses is apparent with a standard aspirin formulation, but seems substantially less when using a highly soluble acetylsalicylate salt.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

An increase in total and low density lipoprotein (LDL) cholesterol concentrations is related to the incidence of cardiovascular heart disease. The purpose of this study was to compare the efficacy and safety of pravastatin, an HMG-CoA reductase inhibitor, versus gemfibrozil, a fibrate, in the treatment of primary hypercholesterolaemia. 855 subjects (males and females, aged between 18 and 70 years) with total cholesterol (TC) concentrations > 240 mg/dl and triglyceride (TG) concentrations < 250 mg/dl were enrolled. After a pretreatment diet period, patients received either pravastatin 20 mg/day (659 patients) or gemfibrozil 1200 mg/day (196 patients). At the end of the 12-week treatment period, reductions in TC (−23%) and LDL-C (−31%) were noted in the pravastatin group. Gemfibrozil reduced TC by 16% and LDL by 20%. High density lipoprotein (HDL) cholesterol concentrations increased in a similar way in the two groups: pravastatin +10%, gemfibrozil +11%. Triglycerides decreased by 14% with pravastatin and by 22% with gemfibrozil. Pravastatin and gemfibrozil were both well tolerated. No significant adverse events or variations in laboratory parameters occurred during this study.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The antihypertensive efficacy and safety of quinapril 20mg plus hydrochlorothiazide 6.25mg were compared over 8 weeks with captopril 50mg plus hydrochlorothiazide 15mg in 52 patients with mild to moderate essential hypertension (27 men and 25 women age 49.7 ± 8.4 years). The study also evaluated the relationship between antihypertensive efficacy and plasma renin activity/blood pressure sensitivity to changes in dietary sodium intake. The combination of quinapril or captopril with hydrochlorothiazide showed similar antihypertensive effects and tolerability. Neither blood pressure salt sensitivity nor renin profile were predictive of blood pressure response to either therapy. These results suggest that the antihypertensive efficacy of an angiotensin converting enzyme inhibitor when administered in fixed ratio with a thiazide diuretic is independent of salt sensitivity in hypertension.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The biological potency of 2 recombinant human granulocyte colony-stimulating factors (rG-CSF) formulated for clinical use (lenograstim and filgrastim) together with a nonmarketedEscherichia coli-derived rG-CSF were compared by duplicate neutrophil colony assays in 3 normal human marrows. Serial doubling dilutions of each rG-CSF (128 to 0.008 ng/ml) were used. Neutrophil colonies were blindly scored at day 14. Lenograstim stimulated neutrophil colony formation at doses 16 times lower than that of the 2 nonglycosylated rG-CSFs and was twice as potent as filgrastim at maximal colony stimulation. Qualitative differences in colony size were also noted. Both nonglycosylated rG-CSFs (filgrastim and research-use rG-CSF) gave inferior qualitative and quantitative results, suggesting that glycosylation gives lenograstim a potency advantage.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS