Systemic exposure to inhaled beclometasone/formoterol DPI is age and body size dependent.

AIM: Prescription of inhaled corticosteroids to children with asthma is recommended at half the nominal dose of adults in order to reduce the risk of systemic side effects. However, there is a lack of pharmacokinetic trials supporting such dose reduction regimens. Therefore, we aimed to compare the systemic exposure to the active ingredients of a fixed dose combination of beclometasone-dipropionate (BDP) and formoterol after dry powder inhaler (DPI) administration in children, adolescents and adults. METHODS: The pharmacokinetic profiles of formoterol and beclometasone-17-monopropionate (B17MP; active metabolite of BDP) were evaluated over 8 h from two independent studies comprising children (6-11yrs, n = 27), adolescents (12-17 yrs, n = 28) and adults (≥18 yrs, n = 30) receiving a single, fixed dose of BDP/formoterol (children: 200 µg/24 µg, adolescents and adults: 400 µg/24 µg) via DPI. RESULTS: The systemic exposure (AUC) for children versus adults was almost doubled for formoterol and similar for B17MP despite the halved BDP dose administered in children. In adolescents the AUC for formoterol and B17MP were approximately one third higher than in adults for both compounds. Upon normalization for the BDP/formoterol dose in the three populations the AUC and peak concentration (C(max)) correlated inversely with age and body surface area of the patients (r ≤ -0.53; p < 0.0001). CONCLUSION: The systemic exposure to the active ingredients of BDP/formoterol administered as DPI correlates inversely with age and body size suggesting that dry powder dosage regimens should be adjusted for age and body size to avoid high systemic drug levels in children.

Collagen- and gelatine-based films sealing vascular prostheses: evaluation of the degree of crosslinking for optimal blood impermeability.

The stiffness as well as the biodegradation rate of collagen and gelatine products can be modulated by performing a number of crosslinking treatments. In many biomedical applications, an optimal degree of crosslinking seems to exist, depending on the mechanical and/or biosynthesis properties of the host site. The aim of this study was to evaluate the optimal degree of crosslinking of collagen and gelatine films, to be used as sealants for vascular prostheses. Various crosslinking treatments, including exposure to aldehydes, dehydrothemal treatment, carbodiimide crosslinking and combinations of them, were performed on collagen and gelatine films, and the resulting increases in stiffness, degree of crosslinking and denaturation temperature were evaluated. Analogue crosslinking treatments were also performed on sealed prostheses, which were then tested for blood leakage. The experimental results showed that a good blood impermeability of both collagen and gelatine films was obtained for crosslinking density of about 1.2-1.3 x 10(-5) mol/cm(3), which could be yielded by a dehydrothermal crosslinking treatment (DHT). In particular, dehydrothermally treated gelatine-coated prostheses were found to perform better than analogue collagen-coated ones. The presence of glycerol in crosslinked collagen films was found to have plasticizing effects, which are likely to facilitate blood impermeability, and to increase the thermal stability of collagen.

First clinical evaluation of ganstigmine in patients with probable Alzheimer's disease.

The objective of this study was to evaluate the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of five fixed doses of ganstigmine (CHF 2819) in patients with probable Alzheimer's disease (AD). This randomized, double-blind, placebo-controlled trial evaluated five dose levels (5, 7.5, 10, 12.5, and 15 mg) administered orally once daily for 7 days. Adverse events and continuous telemetry were collected on successive panels of six patients (five active, one placebo). Acetylcholinesterase, butyrylcholinesterase, and plasma drug levels were measured. A total of 29 patients were randomized and 18 completed the study. A total of seven patients, including five of five in the 12.5-mg panel, discontinued because of adverse events. Four patients were withdrawn administratively from the first panel while an episode of atrial fibrillation (the only serious adverse event) was investigated. This panel was then repeated. Mild, transient headache or nausea were the most commonly reported adverse events. Multiple moderate adverse events in the 12.5-mg panel (including nausea, vomiting, and anorexia) led to the decision not to proceed with a 15-mg panel. Ten milligrams was determined to be the maximum tolerated dose. Ganstigmine exhibited nonlinear pharmacokinetics, was absorbed rapidly, and reached peak concentrations within 1 hour. Acetylcholinesterase inhibition was dose dependent and lasted as long as 24 hours. Ganstigmine, a novel cholinesterase inhibitor, was well tolerated within a dosing range of 5 to 10 mg. Once-daily dosing is supported by data on acetylcholinesterase inhibition.

Study of mepartricin possible interactions with antilipemic drugs. Controlled clinical trials in patients with benign prostatic hyperplasia.

In order to more throughly study mepartricin pharmacodynamic characteristics, 2 groups of 15 patients with BPH and coexistent lipid metabolism disorders were studied in conformity with a sequential experimental design during which also systemic-acting (procetofen) and endoluminal-acting (cholestyramine) fat-lowering drugs were tried. The data obtained confirmed mepartricin specific effect on symptomatology and function in BPH and demonstrated the absence of positive and/or negative pharmacological interactions between the substance in question and the fat-lowering agents tried.

Functional evaluation of new experimental model of microsurgical tubulovasostomy in rat.

The function of a new experimental microsurgical model of tubulovasostomy is evaluated. The model is represented by an end-to-end tubulodeferential anastomosis after removal of the proximal (juxtaepididymal) half of the vas deferens and segmental unfolding of the distal part of the epididymal tubule. Both anastomosed segments are evaluated for responsiveness to norepinephrine and field stimulation. The results are discussed in terms of accurate selection of segments to be anastomosed on the basis of their morphofunctional correlates; in fact, it seems worth replacing the segments removed only with others endowed with equivalent properties.

Cefotaxime for the treatment of gram-positive urinary tract infection.

Urinary tract infections (UTI) due to gram-positive bacteria are fairly uncommon. In order to investigate the efficacy of treatment for UTI secondary to gram-positive rods, we performed a non-comparative study on the effect of cefotaxime in 64 patients with gram-positive UTI. Patients with a history of hypersensitivity to cephalosporins and penicillin as well as patients who had received antibiotic treatment within 48 hours after the administration of cefotaxime, patients with hepatic disease and patients with fatal progressive disease were excluded from the study. UTI was confirmed by positive cultures with a colony count of greater than or equal to 100,000 cfu/ml of gram-positive organisms before treatment with cefotaxime. When sepsis or bacteriuria occurred after two days of hospitalization, the UTI was considered nosocomial. The most common microorganism isolated was Staphylococcus aureus, followed by Streptococcus faecalis. 30% of the patients showed polymicrobic bacteriuria, especially in association with gram-negative bacteria (70%). A high frequency of predisposing factors was present in the urinary tract, mainly obstruction, indwelling catheters, surgery and chronic debilitating diseases. Seven patients developed bacteremia. All patients were treated with cefotaxime i.m. or i.v. at a daily dosage ranging between 4 and 12 g. Urine cultures were repeated five days after the beginning of treatment and again two to three weeks after the end.(ABSTRACT TRUNCATED AT 250 WORDS)