ABSTRACT
Doxofylline (7-(1,3-dioxalan-2-ylmethyl) theophylline) is a novel xanthine bronchodilator which differs from theophylline in that it contains a dioxalane group in position 7. Similarly to theophylline, its mechanism of action is related to the inhibition of phosphodiesterase activities, but in contrast it appears to have decreased affinities towards adenosine A1 and A2 receptors, which may account for its better safety profile. The bronchodilating activities of doxofylline have been demonstrated in clinical trials involving patients with either bronchial asthma or chronic obstructive pulmonary disease. In contrast to other bronchodilators, experimental and clinical studies have shown that the drug is devoid of direct stimulatory effects. This may be of importance because the arrhythmogenic actions of bronchodilators may have a negative impact on the survival of patients with respiratory diseases.
Subject(s)
Arrhythmias, Cardiac/chemically induced , Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Cardiovascular Diseases/chemically induced , Lung Diseases, Obstructive/drug therapy , Phosphodiesterase Inhibitors/therapeutic use , Pulmonary Heart Disease/drug therapy , Theophylline/therapeutic use , Animals , Bronchodilator Agents/chemistry , Bronchodilator Agents/pharmacology , Drug Evaluation, Preclinical , Humans , Phosphodiesterase Inhibitors/chemistry , Phosphodiesterase Inhibitors/pharmacology , Receptors, Purinergic P1/drug effects , Risk Factors , Safety , Theophylline/analogs & derivatives , Theophylline/chemistry , Theophylline/pharmacology , Treatment Outcome , Xanthines/chemistry , Xanthines/pharmacology , Xanthines/therapeutic useABSTRACT
The effects of oral doxofylline (400 mg BID) on bronchial airway mucosa were investigated in 14 patients with chronic obstructive bronchitis. The eligible patients had to have forced expiratory volume in 1 second > 60% of the predicted value and oxygen partial tension > 55 mm Hg. At the onset and the end of the study, bronchial biopsies were performed via a flexible fiberoptic bronchoscope. Chronic inflammation of the airways was graded according to absence of lesions = 0, involvement of 1-10% = 1, 10-50% = 2 and > 50% = 3. After three months of treatment, 57% of patients in the doxofylline group presented absence of lesions, while the remaining 43% exhibited advanced lesions. In the control group, absence of lesions was observed in 14%, while lesions of grade 1, 2 and 3 were visible in 14%, 29% and 43%, respectively. At histological examination, a significant difference in the degree of structural changes was observed in the doxofylline group between baseline and the end of the study (p < 0.03). In conclusion, doxofylline may induce favorable effects on inflammatory changes and altered cell proliferation of the airway mucosa in patients with chronic obstructive bronchitis.
Subject(s)
Bronchitis/drug therapy , Bronchitis/pathology , Bronchodilator Agents/therapeutic use , Lung Diseases, Obstructive/drug therapy , Lung Diseases, Obstructive/pathology , Theophylline/therapeutic use , Bronchi/pathology , Cell Division/drug effects , Female , Humans , Male , Middle Aged , Mucous Membrane/pathology , Theophylline/analogs & derivativesABSTRACT
The aim of the study was to determine the properties of a standardized extract of ginseng root in inducing a higher immune response in vaccination against influenza. Attention was also paid to the common cold in this multicentre, two-arm, randomized, placebo-controlled, double-blind investigation. A total of 227 volunteers who visited 3 private practices in Milan received daily oral capsule doses of either placebo (113) or 100 mg of standardized ginseng extract Ginsana G 115 (114) for a period of 12 weeks within which they received an anti-influenza polyvalent vaccination at week 4. As a result, while the frequency of influenza or common cold between weeks 4 and 12 was 42 cases in the placebo group, it was only 15 cases in the G115 group, the difference being statistically highly significant (p < 0.001). Whereas antibody titres by week 8 rose to an average of 171 units in the placebo group, they rose to an average of 272 units in the G115 group (p < 0.0001). Natural killer (NK) activity levels at weeks 8 and 12 were nearly twice as high in the G115 group as compared to the placebo group (p < 0.0001). In all the volunteers, laboratory values of 24 safety parameters showed no significant differences between the end and the beginning of the 12-week study in either of the groups. There were only 9 adverse events in the study, the principal one being insomnia.
Subject(s)
Common Cold/prevention & control , Drugs, Chinese Herbal/therapeutic use , Influenza, Human/prevention & control , Panax/chemistry , Plants, Medicinal , Adult , Common Cold/immunology , Double-Blind Method , Drugs, Chinese Herbal/adverse effects , Female , Humans , Immunity, Cellular/drug effects , Influenza, Human/immunology , Male , Middle Aged , VaccinationABSTRACT
In the present study, besides the clinical activity and safety of rokitamycin in patients with episodes of breakthrough chronic bronchitis, its influence on the production of secretory immunoglobulins of group A (sIgA) at the bronchial level was studied. Fifteen patients (12M, 3F), of mean age 51.0 years 7.0 SD were treated with rokitamycin in 400 mg tablets (2 tabs/day) for 10 days. The results attained confirmed the therapeutic efficacy of rokitamycin, with a clear improvement of symptoms already by the 5th day. The levels of sIgA in bronchial secretions showed on the 10th day a statistically significant increase, superior to that reported in the literature for other antibiotics, passing from 18.2 microg/mL 0.9 SEM at the baseline to a value of 19.4 microg/mL 0.9 SEM. The high therapeutic safety of rokitamycin should be emphasised: it determined no variations in the laboratory parameters considered; in the course of treatment no patients suffered adverse events. The results attained, which confirm the clinical efficacy of rokitamycin and complete its pharmacodynamic profile, allow us to advise the use of this macrolid with 16 carbon atoms in acute infective pathologies of the respiratory tract.
ABSTRACT
To determine the efficacy in vivo of pefloxacin and ciprofloxacin in the treatment of acute infectious bronchopneumopathies, 90 patients, suffering from acute exacerbation of chronic bronchitis and with no known allergies to quinolones, were admitted to the study. Patients were randomly divided into three groups of 30; the first group was dosed with pefloxacin 800 mg i.v. every 24 hours; the second group with pefloxacin 800 mg per os every 24 hours and the third with 500 mg per os of ciprofloxacin every 12 hours. Blood and bronchial secretion samples were simultaneously collected 2, 4, 8, 12, 14 and 24 hours after the first daily dose of antibiotic. Serum and bronchial secretion concentrations of pefloxacin and ciprofloxacin were determined by using a microbiological agar disk diffusion assay, employing Escherichia coli Kp 712 as test organism. Eradication of responsible microorganisms (Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis) were achieved in 98% of patients around 72 hours post treatment. Generally, both antibiotics expressed similar bactericidal properties when orally administered, while intravenous administration of pefloxacin displays a more rapid antibacterial action in comparison with the oral administration schedules. Maximal concentrations of both drugs in bronchial secretion were recorded at the same time after treatment (4 hours), with concentrations of about 2.5 micrograms/ml. Pefloxacin, having a longer half-life, was found 24 hours post-treatment with plasma concentrations of 1.5 micrograms/ml following a single oral dose of 800 mg. Ciprofloxacin, having a shorter half-life, showed a peak of about 1 microgram/ml, 12 hours after administration (500 mg/12 hours/os).
Subject(s)
Bacterial Infections/drug therapy , Ciprofloxacin/therapeutic use , Pefloxacin/therapeutic use , Respiratory Tract Infections/drug therapy , Adult , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Bronchi/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Chronic Disease , Ciprofloxacin/blood , Ciprofloxacin/pharmacokinetics , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Haemophilus influenzae/drug effects , Humans , Male , Microbial Sensitivity Tests , Moraxella catarrhalis/drug effects , Pefloxacin/blood , Pefloxacin/pharmacokinetics , Respiratory Tract Infections/metabolism , Respiratory Tract Infections/microbiology , Staphylococcus aureus/drug effectsABSTRACT
The efficacy and tolerability of brodimoprim OD versus norfloxacin BID were studied in patients affected by bacterial urinary tract infections. The study was performed in 203 patients divided into two parallel randomized groups orally given either brodimoprim 400 mg OD on the first day followed by 200 mg OD for 2 days, or norfloxacin 400 mg BID respectively. The efficacy of treatment was evaluated by the bacterial cultures, tolerability, analysis of signs and symptoms, a complete physical examination and from laboratory data. The results showed that brodimoprim and norfloxacin in the majority of patients resulted in a reduction of fever and symptoms caused by the infective process. Of the 103 patients enrolled in the brodimoprim OD group, 99 had a complete course of therapy with a positive outcome. There was only one case of failed treatment and 3 cases which could not be evaluated because of voluntary interruption of treatment. Of the 100 patients treated with norfloxacin BID, 94 completed therapy with a positive clinical outcome and there were 4 cases of treatment failure. Thus the efficacy of brodimoprim OD appears comparable to that of norfloxacin BID in the treatment of urinary tract infections.
Subject(s)
Anti-Infective Agents/therapeutic use , Folic Acid Antagonists/therapeutic use , Norfloxacin/therapeutic use , Trimethoprim/analogs & derivatives , Urinary Tract Infections/drug therapy , Adult , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Clinical Trials, Phase III as Topic , Female , Folic Acid Antagonists/administration & dosage , Folic Acid Antagonists/adverse effects , Humans , Male , Middle Aged , Norfloxacin/administration & dosage , Norfloxacin/adverse effects , Trimethoprim/administration & dosage , Trimethoprim/adverse effects , Trimethoprim/therapeutic use , Urinary Tract Infections/microbiologyABSTRACT
Brodimoprim, a structural analogue of trimethoprim, is a long acting broad spectrum antibacterial agent characterized by a good pharmacokinetic profile, allowing once daily (OD) administration. The aim of this study was to investigate the penetration of brodimoprim into bronchial mucosa, bronchial secretion and middle ear effusion, in order to evaluate the efficacy of the antibiotic in respiratory tract infections. The study was performed in patients affected by chronic bronchitis having to undergo diagnostic bronchoscopy (n = 26), in patients affected by exacerbation of chronic bronchitis with purulent or mucopurulent secretions (n = 10), and in patients affected by otitis media with eardrum perforation (n = 28). Patients were orally treated with 400 mg of brodimoprim (single dose). Samples of serum, bronchial mucosa, bronchial secretion and middle ear effusion were collected in the separate series of patients above mentioned, at different times after drug administration. Brodimoprim determinations were performed by a microbiological method using Bacillus subtilis ATCC 6633 as test microorganism. Brodimoprim reached the highest concentration in serum 4 h after administration and was still detectable at 24th hour. In bronchial mucosa and in bronchial secretion the peaks were reached at 8th hour (9.7 +/- 5.3 mg/kg and 4.57 +/- 1 mg/l respectively) while in middle car effusion were reached at 4th hour (4.8 +/- 2.5 mg/l). The drug was still detectable at antibacterial concentrations, both in infected fluids and in tissue samples, 24 hours after administration (4.3 +/- 1.8 mg/kg in bronchial mucosa; 3.5 +/- 0.66 mg/l in bronchial secretions; 3 +/- 0.6 mg/l in middle ear effusion).(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Bronchi/metabolism , Bronchitis/drug therapy , Bronchitis/metabolism , Otitis Media with Effusion/drug therapy , Otitis Media with Effusion/metabolism , Trimethoprim/analogs & derivatives , Administration, Oral , Adult , Aged , Chronic Disease , Exudates and Transudates/metabolism , Female , Humans , Male , Middle Aged , Trimethoprim/pharmacokinetics , Trimethoprim/therapeutic use , Tympanic Membrane Perforation/drug therapy , Tympanic Membrane Perforation/metabolismABSTRACT
The pharmacokinetics of rufloxacin, after repeated doses, was evaluated in 12 elderly patients with lower respiratory tract infections. Patients were given a single loading dose of 400 mg on the first day of treatment and single daily maintenance doses of 200 mg for the next 6-9 days. Serum concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at regular intervals during treatment and fitted to a one-compartment open model for repeated doses. The maximum serum concentration after the first dose was 6.46 +/- 1.06 (mean +/- SEM) micrograms/ml and was reached in 4.3 +/- 0.8 h after the first administration. The elimination half-life was 28.7 +/- 4.1 h. The area under the serum levels-time curve from 0 to 24 h was 103 +/- 14 micrograms/h/ml after the first dose. On the last day of observation it increased to 155 +/- 28 micrograms/h/ml, with a mean extent of accumulation of 2.3 +/- 0.3 times. The elimination half-life was comparable to those in other studies in healthy young subjects, while plasma levels were about 80% higher. These results suggest that in elderly patients elevated drug concentrations may be reached in the serum. Although no untoward reactions related either to the drug concentration in serum or the dose have been noted with rufloxacin, this patient population should nevertheless be monitored carefully for adverse effects.
Subject(s)
Anti-Infective Agents/pharmacokinetics , Fluoroquinolones , Quinolones/pharmacokinetics , Respiratory Tract Infections/metabolism , Aged , Aged, 80 and over , Anti-Infective Agents/therapeutic use , Chromatography, High Pressure Liquid , Female , Half-Life , Humans , Male , Middle Aged , Models, Biological , Quinolones/therapeutic use , Respiratory Tract Infections/drug therapy , Spectrophotometry, UltravioletABSTRACT
We studied the clinical and instrumental modifications of 20 patients (mean age: 67.95 +/- 1.23 years; 13 males, 7 females) suffering from COPD (less than 65% theoretical FEV1), during treatment with bamiphylline. At basal time, and after 1, 2, 3, 4, and 6 months of therapy we performed a clinical and spirometric examination. All spirometric parameters (FEV1, VC, MEF25-75, Tiffeneau Index) increased significantly (p less than 0.01 - ANOVA1) since the first control performed after 1 month of treatment. This trend was confirmed in the successive controls. Analogue results were observed for emogasanalytical (P-CO2-PO2) and clinical (cough and dyspnoea) parameters. During the experimental research we did not observe side effects due to the xanthine-derivative (bamiphylline) under study or modifications of the main haematochemical tests. Therefore we believe that bamiphylline must be considered an effective therapeutic tool for COPD therapy.
Subject(s)
Bronchodilator Agents/therapeutic use , Lung Diseases, Obstructive/drug therapy , Theophylline/analogs & derivatives , Aged , Dyspnea/drug therapy , Dyspnea/etiology , Female , Humans , Lung Diseases, Obstructive/complications , Male , Respiratory Function Tests , Theophylline/therapeutic useABSTRACT
The pharmacokinetic parameters of monosialotetrahexosylganglioside (GM1) have been determined in healthy volunteers at 3 dose levels: 100, 200, 300 mg. Each dose was administered to separate groups of 12 volunteers. GM1 levels were determined in plasma, urine, and faeces by a method based on the property of the cholera toxin beta subunit to react specifically with GM1 ganglioside. A non-compartmental model was applied to determine standard pharmacokinetic parameters. The average AUC increased with dose (1002 +/- 121.2, 1306 +/- 146.1, 3155 +/- 121.6 micrograms mL-1 h after 100, 200, 300 mg, respectively). Plasma clearance was less than 3 mL min-1 and the distribution volume was close to the plasma volume (on average between 4.3 and 7.2 L). Mean residence time was about 43 h for all doses. GM1 was not detected in urine, while in faeces the amount of GM1 determined was similar to the baseline values obtained before dosing.
Subject(s)
G(M1) Ganglioside/pharmacokinetics , Adult , Blood Pressure/drug effects , Feces/chemistry , Female , G(M1) Ganglioside/administration & dosage , G(M1) Ganglioside/adverse effects , Half-Life , Heart Rate/drug effects , Humans , Injections, Intravenous , Male , Respiration/drug effectsABSTRACT
The absorption of iron after oral administration of 80 mg iron--protein--succinylate complex was evaluated by determining serum iron concentrations in 10 patients who had undergone total gastrectomy more than 1 year before and were suffering from hypochromic anaemia. Serum iron concentrations in these patients were no different from those obtained in 10 'normal' hypochromic anaemic patients.
Subject(s)
Ferric Compounds/metabolism , Gastrectomy , Intestinal Absorption , Metalloproteins/metabolism , Succinates/metabolism , Administration, Oral , Anemia, Hypochromic/metabolism , Humans , Iron/blood , Metalloproteins/administration & dosage , Succinates/administration & dosageABSTRACT
The number of extra European subjects coming to our country, in the last twenty years, is increased. This fact has contributed to enlarge the number of new cases of tuberculosis. In the present work we analyzed 54 extra European and 116 Italian patients with pulmonary tuberculosis observed in the last six years in our institute. The diagnosis was established by finding acid-fast bacilli in sputum and by clinical and radiographic patterns. We found that extra European subjects show disseminated and ulcerated forms in about 89% against approximately 40% viewed in Italian patients; while the cases of noncavitary tb in immigrants were about 11% against 60% in Italian population.
Subject(s)
Emigration and Immigration , Tuberculosis, Pulmonary/epidemiology , Adolescent , Adult , Aged , Emigration and Immigration/statistics & numerical data , Female , Humans , Italy/epidemiology , Lung/diagnostic imaging , Male , Middle Aged , Mycobacterium tuberculosis/isolation & purification , Radiography , Sputum/microbiology , Tuberculosis, Pulmonary/diagnosisABSTRACT
Forty-five patients with inoperable non small cell lung carcinoma were treated according to a sequential polychemotherapeutic regimen with cisplatin-vinblastine (A), cyclophosphamide-etoposide (B), and adriamycin-vincristine (C). Patients were evaluated every two cycles. Ten patients (22.2%) showed a partial response with a mean duration of 20 weeks, and mean survival of 50.8 weeks. It is remarkable that, among them, 6 patients (13.3%) lived over 12 months and three (6.6%) over 18 months. The mean survival for all patients was 35.7 weeks. Toxicity was acceptable and reversible.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Drug Administration Schedule , Female , Humans , Lung Neoplasms/mortality , Male , Middle AgedSubject(s)
Bacteria/drug effects , Bronchi/microbiology , Bronchitis/drug therapy , Ceftriaxone/pharmacology , Piperacillin/pharmacology , Aged , Bacteria/isolation & purification , Bronchitis/microbiology , Ceftriaxone/administration & dosage , Clinical Trials as Topic , Haemophilus influenzae/drug effects , Haemophilus influenzae/isolation & purification , Humans , Injections, Intramuscular , Microbial Sensitivity Tests , Middle Aged , Piperacillin/administration & dosage , Random Allocation , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/isolation & purificationABSTRACT
The bactericidal quotient (BQ) assessed in the site of infection represents an essential parameter for evaluating the real bactericidal potency of an antibiotic in vivo. The assessment and knowledge of BQ values allow us to set up a more accurate and appropriate antibacterial therapy. The two drugs--ceftriaxone (Rocephin) and imipenem plus cilastatin (Tienam)--that have been taken into consideration in this study, having a similar antibacterial spectrum though with different kinetics, may have the same BQ values in bronchial secretion versus Haemophilus influenzae, Klebsiella pneumoniae and Streptococcus pneumoniae, when administered at different dosages, i.e. ceftriaxone 1 g (i.v.) every 24 h, imipenem 0.5 g (i.v.) every 8 h.
Subject(s)
Bronchial Diseases/drug therapy , Ceftriaxone/pharmacology , Cilastatin/pharmacology , Imipenem/pharmacology , Sputum/microbiology , Aged , Bronchial Diseases/microbiology , Ceftriaxone/pharmacokinetics , Drug Administration Schedule , Drug Combinations , Haemophilus Infections/drug therapy , Haemophilus influenzae/drug effects , Humans , Imipenem/pharmacokinetics , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Middle Aged , Sputum/analysis , Streptococcal Infections/drug therapy , Streptococcus pneumoniae/drug effectsABSTRACT
The pharmacokinetics of ribavirin and aminophylline (theophylline ethylenediamine) after oral administration in healthy adults and in children suffering from viral infections of the respiratory tract, with superimposition of bronchial asthma or asthmatic syndrome, was studied. By the prompt-release formulation of aminophylline the hematic peak is reached within the first 30 min (9.03 micrograms/ml) from intake, whereas by the sustained-release formulation the peak is reached only within the 5th hour (8.5 micrograms/ml). After administration of ribavirin no interferences with the clearance of theophylline both in adults and children were noted.
Subject(s)
Aging/metabolism , Ribavirin/pharmacology , Ribonucleosides/pharmacology , Theophylline/blood , Aged , Child , Delayed-Action Preparations , Drug Interactions , Female , Humans , Immunoenzyme Techniques , Male , Middle Aged , Theophylline/administration & dosageABSTRACT
Sixty patients affected by chronic obstructive lung disease (COLD) in relapse were treated with erythromycin and aminophylline. The patients were divided into three groups: Group A received 2 g erythromycin and 1200 mg aminophylline daily, and Group B and C received 2 g erythromycin with respectively 800 mg and 600 mg of aminophylline daily, administered as two oral doses in each case. On day 5 of therapy, we chromatographically evaluated aminophylline in a serum sample taken two hours after morning drug administration which corresponds to the peak plasma level. We also evaluated certain biohumoral, microbiological, radiological and electrocardiographic parameters both before and after therapy. Statistical analysis of the data was performed by the Student's t test. Our data confirm that 600-800 mg oral aminophylline administered simultaneously with erythromycin induce an improvement in the respiratory function of patients with relapsed COLD without elevating blood aminophylline levels and without side-effects.