Biomedical subjects

A Macciocchi

Publications and source records attributed to A Macciocchi.

17 recordsLinked to original sources

PubMed2006

A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy.

BACKGROUND: This pivotal phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: Patients were randomized to a single intravenous dose of palonosetron 0.25 mg or 0.75 mg, or ondansetron 32 mg prior to HEC. Dexamethasone pre-treatment (with stratification) was used at investigator discretion. The primary efficacy endpoint was the proportion of patients with complete response (CR) during the first 24 h post-chemotherapy (acute phase). RESULTS: In the intent-to-treat analysis (n = 667), palonosetron 0.25 mg and 0.75 mg were at least as effective as ondansetron in preventing acute CINV (59.2%, 65.5%, and 57.0% CR rates, respectively); CR rates were slightly higher with palonosetron than ondansetron during the delayed (24-120 h) and overall (0-120 h) phases. Two thirds of patients (n = 447) received concomitant dexamethasone. Patients pre-treated with palonosetron 0.25 mg plus dexamethasone had significantly higher CR rates than those receiving ondansetron plus dexamethasone during the delayed (42.0% versus 28.6%) and overall (40.7% versus 25.2%) phases. Palonosetron and ondansetron were well tolerated. CONCLUSIONS: Single-dose palonosetron was as effective as ondansetron in preventing acute CINV following HEC, and with dexamethasone pre-treatment, its effectiveness was significantly increased over ondansetron throughout the 5-day post-chemotherapy period.

Adult↗

PubMed2004

Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study.

BACKGROUND: Although currently available 5-hydroxytryptamine type 3 receptor (5-HT3) antagonists are effective, not all patients receiving these agents achieve adequate control of chemotherapy-induced nausea and vomiting (CINV). Palonosetron, a potent and highly selective 5-HT3 antagonist with a strong affinity for 5-HT3 and a prolonged plasma elimination half-life, may provide a longer duration of action than other approved agents. PATIENTS AND METHODS: One hundred and sixty-one patients were randomly assigned to receive a single intravenous bolus dose of palonosetron (0.3, 1, 3, 10, 30 or 90 microg/kg) before administration of highly emetogenic chemotherapy, with no pretreatment with corticosteroids. RESULTS: The four highest doses of palonosetron were similarly effective during the first 24 h, producing clearly higher complete response (CR) (no emesis, no rescue medication) rates in the 3, 10, 30 and 90 microg/kg groups (46%, 40%, 50% and 46%, respectively) than in the 0.3-1 microg/kg group (24%) of evaluable patients (n = 148). The 3 microg/kg dose was identified as the lowest effective dose. A single dose of palonosetron showed prolonged efficacy in preventing delayed emesis, with approximately one-third of patients who received palonosetron 10 or 30 microg/kg maintaining a CR throughout the 7-day period following chemotherapy administration. Dose-proportional increases in pharmacokinetic parameters and a long plasma half-life (43.7-128 h) were observed. Palonosetron was well-tolerated, with no dose-response effect evident for the incidence or intensity of adverse events. CONCLUSIONS: Palonosetron is an effective and well-tolerated agent for the prevention of CINV following highly emetogenic chemotherapy, with 3 and 10 microg/kg identified as the lowest effective palonosetron doses.

Adult↗

PubMed2003

Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron.

BACKGROUND: Although all first-generation 5-HT(3) receptor antagonists demonstrate efficacy in preventing acute chemotherapy-induced nausea and vomiting (CINV), effective prevention of delayed CINV has not yet been achieved. This study compared the efficacy and tolerability of palonosetron, a novel, second-generation 5-HT(3) receptor antagonist, with ondansetron. PATIENTS AND METHODS: In this multicenter, randomized, double-blind, stratified, phase III study, 570 adult cancer patients were randomized to receive a single i.v. dose of palonosetron 0.25 mg, palonosetron 0.75 mg or ondansetron 32 mg, each administered 30 min before initiation of moderately emetogenic chemotherapy. The primary end point was the proportion of patients with no emetic episodes and no rescue medication [complete response (CR)] during the 24 h after chemotherapy administration (acute period). Secondary end points included efficacy in treatment of delayed CINV (</=5 days post-chemotherapy) and overall tolerability. RESULTS: 563 patients were evaluable for efficacy. CR rates were significantly higher (P <0.01) for palonosetron 0.25 mg than ondansetron during the acute (0-24 h) (81.0% versus 68.6%, respectively), delayed (24-120 h) (74.1% versus 55.1%) and overall (0-120 h) (69.3% versus 50.3%) periods. CR rates achieved with palonosetron 0.75 mg were numerically higher but not statistically different from ondansetron during all three time intervals. Both treatments were well tolerated. CONCLUSIONS: A single i.v. dose of palonosetron 0.25 mg was significantly superior to i.v. ondansetron 32 mg in the prevention of acute and delayed CINV.

Adult↗

PubMed2001

Double-blind study comparing the long-term efficacy of the COX-2 inhibitor nimesulide and naproxen in patients with osteoarthritis.

This double-blind one-year study compares the long-term efficacy and safety of nimesulide with naproxen in patients with osteoarthritis (OA) of the knee or hip. Patients were randomised to nimesulide 100 mg twice daily (n = 183) or naproxen 250 mg morning, 500 mg evening (n = 187). The primary efficacy variable was change in pain intensity (WOMAC A scale) at 6 months. Nimesulide tablets showed at least equivalent efficacy to naproxen tablets in reducing pain intensity at 6 and 12 months (nimesulide -22.5% at 6 and 12 months; naproxen -22.4% at 6 months, -19.9% at 12 months; non-inferiority proven). At 6 months the investigator assessed efficacy as 'good' or 'excellent' in 59.3% of nimesulide and 56.4% of naproxen-treated patients, with corresponding values for patient assessment of 57% and 52.7%. Both treatments were well tolerated, with fewer related gastrointestinal adverse events reported with nimesulide (77 cases, 47.5%) than with naproxen (96 cases, 54.5%). This study shows nimesulide to be as effective as naproxen in the long-term treatment of OA and to be associated with fewer gastrointestinal side-effects.

Adult↗

PubMed1998

The effect of nimesulide versus placebo on hemostasis in healthy volunteers.

OBJECTIVE: The primary objective was to evaluate the effect of 7 days treatment with nimesulide on bleeding time. Blood coagulation, von Willebrand factor and platelet aggregation ex vivo were investigated as a secondary objective. METHOD: A randomised, double-blind, placebo-controlled, parallel group, single centre study performed on 20 healthy male volunteers who received either placebo or nimesulide 100 mg twice daily for 7 days. Bleeding time, platelet count and platelet aggregation, thromboplastin time (prothrombin time), activated partial thromboplastin time, fibrinogen, Factor VIII:C, vWF:Ag, vWF:RCof and platelet-rich plasma aggregation following stimulation with adenosine 5'-diphosphate, collagen, arachidonic acid, ristocetin, thrombin and thrombin receptor-activating peptide were measured at baseline (day 0), and then 3 h after the first (day 1) and last (day 7) treatment. RESULTS: The bleeding times for all subjects remained within the normal range throughout the study period, with no significant differences between the two treatment groups. There were no significant changes from baseline in platelet aggregation studies or in any of the other haemostasis tests, with no significant differences between the two groups. No clinically significant adverse events were reported or observed. CONCLUSIONS: Daily administration of 200 mg nimesulide for 7 days neither prolongs bleeding time nor modifies any of the other haemostasis variables measured. The lack of interactions with important haemostatic mechanisms suggests that nimesulide may also be used in patients with bleeding problems. This expectation has still to be confirmed by clinical experience.

Adult↗

PubMed1994

Double-blind study evaluating by endoscopy the tolerability of nimesulide and diclofenac on the gastric mucosa in osteoarthritic patients.

The gastric tolerability of nimesulide, a new nonsteroidal anti-inflammatory drug (NSAID), was compared with diclofenac, an established NSAID for the treatment of osteoarthritis (OA). A randomised, double-blind parallel group study was undertaken comparing the tolerability and efficacy of nimesulide (100 mg bds) with diclofenac (50 mg tds) over a one month period. Gastroduodenal endoscopy revealed that after 30 days 4 patients had developed ulcers (1 nimesulide patient) and 6 patients had developed erosions (4 nimesulide patients). However, there was no statistically significant difference between the two treatments. Both drugs were clinically very well tolerated and only 10 patients withdrew from the study due to adverse events (5 in each group). Efficacy was assessed by measuring pain on visual analogue scales, by means of the functional index of Lequesne and by scoring spontaneous pain, pain on passive movement and functional impairment. Nocturnal pain was also checked. All efficacy parameters showed a significant improvement during the study without any observed treatment differences.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1994

Multi-centre double-blind study to define the most favourable dose of nimesulide in terms of efficacy/safety ratio in the treatment of osteoarthritis.

A parallel group study for one month of 392 patients was undertaken to define the optimal dose of nimesulide for the treatment of painful osteoarthritis (OA). By the final visit, the mean values for pain intensity for the nimesulide groups (50 mg, 100 mg and 200 mg bd) were similar and significantly lower than the mean for the placebo group. The onset of analgesia was rapid and continued throughout the 12-hour period after drug intake, a significant analgesic effect was demonstrated with nimesulide 100 mg and 200 mg within 1.5 hours. The patients' and the physicians' overall judgements of the drug efficacy demonstrated significant differences between the treatment groups with the most successful outcomes occurring with nimesulide 100 mg and 200 mg. Nimesulide 50 mg and 100 mg were generally well-tolerated but at the highest dose level, nimesulide 200 mg, the incidence of adverse events was greater although not significantly. Results of this study demonstrate nimesulide 100 mg twice daily to be the optimal dose for the treatment of OA.

Acetaminophen↗

PubMed1993

Nimesulide binding to components within blood.

The binding of nimesulide within human serum to isolated proteins and to erythrocytes was studied by equilibrium dialysis. Within the range of therapeutic concentrations, nimesulide was 99% bound to serum involving a nonsaturated process (NKA = 91). This binding was almost identical to binding of nimesulide to serum albumin (NKA = 95). Physiological concentrations of free fatty acids did not affect binding of nimesulide to serum albumin. The retention of nimesulide by erythrocytes suspended in buffer was moderate (67%), although in whole blood no erythrocyte binding was observed because of the greater affinity of this drug for serum. Over the range of therapeutic concentrations (2.5 to 63 mumol/L), the free fraction of nimesulide in serum remains constant. Serum binding was decreased in samples obtained from patients with renal failure or hepatic cirrhosis associated with hypoalbuminaemia and hyperbilirubinaemia, respectively. At therapeutic concentrations, the binding of nimesulide was unaffected by warfarin, cefoperazone, furosemide (frusemide), glibenclamide, tamoxifen or digitoxin. However, valproic acid and fenofibrate (80 mumol/L) may displace nimesulide. 4-Hydroxy-nimesulide, the principal metabolite, significantly increased the free fraction of nimesulide. Although methotrexate had no effect on the free fraction of nimesulide, the free fraction of methotrexate was significantly increased in the presence of nimesulide. The present study also demonstrated 2 distinct nimesulide binding sites (site I and site II) on serum albumin (10 mumol/L) with different affinities: site II KA = 3.57 x 10(5) L/mol and site I KA = 1.24 x 10(5) L/mol. Interaction studies using markers that bind specifically to site I (warfarin and azapropazone) and site II (diazepam and ibuprofen) indicated that nimesulide binds to site II with higher affinity and to a lesser extent to site I.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1993

Controlled clinical investigation of acute analgesic activity of nimesulide in pain after oral surgery.

A double-blind study was conducted to determine the dose-effect relationship of nimesulide and to compare the acute analgesic activity of this agent with that of placebo and niflumic acid. Patients undergoing extraction of an impacted third molar were randomised into 4 groups (nimesulide 100mg; nimesulide 200mg; niflumic acid 250mg and placebo). They were instructed to take their allocated treatment after the onset of pain, and to record the pain severity and relief during the following 6 hours. 134 patients were evaluated. There were significant differences between groups for each time of observation/efficacy parameter (Kruskal-Wallis test). Pairwise comparison (Duncan's test) showed that all 3 active medications were significantly different from the placebo. No substantial differences were found between any of the active treatments. Analogous results were obtained when the amount of rescue drug used (paracetamol) was compared. More positive judgements were reported by patients treated with an active compound than by those taking placebo.

Adolescent↗

PubMed1993

Renal effects of nimesulide in furosemide-treated subjects.

In clinical settings where effective plasma volume is decreased, nonsteroidal anti-inflammatory drugs (NSAIDs) may induce acute renal failure. We have evaluated the effects of single and repeated doses of nimesulide on renal haemodynamics and electrolyte excretion in 8 healthy volunteers during a prolonged course of furosemide (frusemide). Under these study conditions, renal prostaglandin synthesis is expected to be elevated, with renal function being dependent upon increased levels of prostaglandins. Nimesulide induced an acute but transient decrease in indices of renal haemodynamics. Furosemide-induced increases in plasma renin activity and aldosterone levels were blunted, and urinary excretion of prostaglandin E2 was markedly reduced by nimesulide. The magnitude and time course of the natriuretic, kaliuretic and diuretic effects of furosemide were attenuated by nimesulide. Although the transient nature of the observed renal haemodynamic changes suggests that the risk of developing acute renal failure is small, the rise should be taken into account in patients with renal dysfunction. Sodium and potassium retention, and the blunting of the diuretic-induced electrolyte excretion, could be of clinical relevance. Nimesulide appears, therefore, to share the prostaglandin-dependent renal effects of other NSAIDs.

Adult↗

PubMed1993

Antioxidant profile of nimesulide, indomethacin and diclofenac in phosphatidylcholine liposomes (PCL) as membrane model.

An in vitro assay based on the oxidation of phosphatidylcholine liposomes (PCL) with which we can distinguish the anti-HO zero activity from the antilipoperoxidant (R zero, ROO zero, RO zero) has been developed for testing the free-radical-scavenging ability of antiinflammatory drugs. PCL were exposed to a flux of hydroxyl radicals generated by water sonolysis for different periods, and the spontaneous lipid peroxidative phenomenon (propagation and breakdown phases) was followed for the subsequent 24 hours. Lipid peroxidation was assayed by simultaneous measurements of a) conjugated dienes, by UV spectroscopy (absorbance and second derivative at 233 nm), b) loss of lipid substrate (PC), by HPLC, and c) breakdown products (total carbonyl functions as 2,4-dinitrophenylhydrazones). Diclofenac, nimesulide and indomethacin, added to PCL at the starting of the different stages of lipid peroxidation, were tested for their overall and specific anti-radical properties. All the drugs exhibited a remarkable scavenging activity against oxy and lipid radicals, determined as percent inhibition of the formation of conjugated dienes, at concentrations easily attainable in vivo (IC50:diclofenac 2.5 microM, nimesulide 4.92 microM, indomethacin 6.85 microM), diclofenac being the most effective in quenching the R zero and ROO degree species responsible for the propagation phase. By contrast, the antioxidant activity of nimesulide and indomethacin, less potent as alkyl and peroxyl radical scavengers, is due to their ability to restrain the induction phase of the radical chain reaction mediated by hydroxyl radicals (IC50:nimesulide 1.85 microM, indomethacin 3.57 microM).

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1992

Analysis of uterine contractility after administration of the non-steroidal anti-inflammatory drug nimesulide.

To study the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on uterine contractility in different parts of the uterus and on the direction and velocity of propagation of the activity, intra-uterine pressure (IUP) was measured simultaneously in 10 dysmenorrheic and 5 eumenorrheic patients with two microtransducer catheters at two locations (30 mm apart) before and after taking nimesulide, a newly developed NSAID. The uterus developed higher pressure cycles in the fundus than in the isthmus, in both eumenorrheic and dysmenorrheic conditions. Nimesulide did not affect either the active pressure (AP) or the direction and velocity of propagation of the activity, though it alleviated pain significantly. In dysmenorrheic patients, resting pressure (RP) is at a high level only in the fundus. The velocity of propagation ranged from 12 to 19 mm/s. The mathematical probability of procervical activity (1.0 if all procervical; 0.0 if all profundal), and thus the transport, was 0.59 in eumenorrheic and 0.68 in dysmenorrheic patients, the average for the whole series being 0.65. The luminal content (menstrual blood) moves in the cervical direction much more slowly than would be expected on the basis of simple calculations of velocity (velocity vector) of propagation.

Adult↗

PubMed1991

Distribution of oral nimesulide in female genital tissues.

Nimesulide is a non-steroidal anti-inflammatory agent which has proved to be effective in reducing menstrual discomfort in dysmenorrhoeaic women. To determine the concentrations of this drug in the uterus (fundus, cervix), oviduct, and ovaries and to correlate these findings with plasma concentrations, a single oral dose of 100 mg nimesulide was administered 1 to 6 h before surgery to 12 women undergoing hysterectomy and salpingo-oophorectomy, mainly for fibroids. Tissue samples were taken, concentration of nimesulide measured by HPLC, and findings compared with plasma concentrations. One patient not undergoing treatment served as control. Nimesulide concentration in the tissues studied was highest 3 h after administration, as expected from the drug's pharmacokinetic profile. The highest tissue/plasma ratio (0.5) was also found at that time. Average tissue concentrations at 1, 2, 3, and 6 h after drug intake ranged from 0.3 to 1.8 micrograms g-1, and plasma concentrations from 2.6 to 4.1 micrograms ml-1. Nimesulide was evenly distributed in the tissues studied.

Administration, Oral↗

PubMed1990

Effect of flutoprazepam on skills essential for driving motor vehicles.

The effects of the 1,4-benzodiazepine derivative flutoprazepam on the skills essential for driving motor vehicles were tested 2.5 h after intake of 1 x 2 mg and 1 x 4 mg, comparing with placebo. 18 healthy subjects who had homogeneous results in psychological/physical tests took part in the study. The study had a double-blind, randomized crossover design with 7-day washout periods. 2.5 h after intake of 4 mg flutoprazepam, the ability to drive was impaired. Only a very slight reduction in skill was found at the same time under the influence of 2 mg of the drug.

Adult↗

PubMedDate not supplied

Acute salpingitis and thiamphenicol: a microbiologic and therapeutic study.

Eighty-five sexually active women with clinically suspected adnexitis and illness severe enough to require hospitalization were studied. The clinical diagnosis, based on anamnestic data and physical and pelvic examination, was confirmed by laparoscopy and by cultures for aerobic and anaerobic bacteria and for Chlamydia in both cervical canal and intraperitoneal secretions. A ten-day course of thiamphenicol was begun on an empirical basis after laparoscopy. The results showed that fever, an elevated erythrocyte sedimentation rate, and leukocytosis are unreliable diagnostic parameters and that laparoscopy in conjunction with microbial cultures is the only method by which a definite etiologic diagnosis can be established. Positive results of cultures of specimens from the cervical canal are sufficient for the diagnosis of infection due to Neisseria gonorrhoeae, whereas positive culture results for specimens from the intraperitoneal cavity are necessary for the diagnosis of infection caused by Chlamydia trachomatis. Primary treatment with thiamphenicol was successful in 77 (91%) of the 85 patients. Thus, thiamphenicol proved to be effective in the treatment of acute adnexitis.

Acute Disease↗

PubMedDate not supplied

Brodimoprim versus amoxicillin in the treatment of acute sinusitis.

A new dihydrofolate inhibitor, brodimoprim, was compared with amoxicillin in the treatment of acute sinusitis in a general practice controlled study. Eighty adult outpatients with acute sinusitis were randomly assigned to receive 200 mg of brodimoprim once daily or 750 mg of amoxicillin thrice daily for seven to 10 days. The mean duration of treatment was 9.2 days in the brodimoprim group and 9.1 days in the amoxicillin group. In most patients the symptoms of sinusitis had disappeared by day 5 of treatment. The reduction in symptom scores was more marked in the brodimoprim-treated patients than in the amoxicillin-treated patients. Bacteriologic examinations after treatment were performed in 20 patients of each treatment group. At completion of treatment, the causative pathogen had been eradicated in 14 of 20 patients treated with brodimoprim and in 12 of 20 patients treated with amoxicillin. Treatment side effects were reported by two brodimoprim-treated patients (skin reactions) and by six amoxicillin-treated patients (gastrointestinal distrubances or skin reactions). The results indicate that brodimoprim is safe and effective in the treatment of acute sinusitis in adults.

Acute Disease↗

PubMedDate not supplied

Comparative efficacy and safety of the non-steroidal anti-inflammatory drugs nimesulide and diclofenac in patients with acute subdeltoid bursitis and bicipital tendinitis.

The efficacy and tolerability of nimesulide, a non-steroidal anti-inflammatory drug (NSAID) 100 mg twice daily were compared with diclofenac 75 mg b.i.d. in short term treatment of acute shoulder (acute subdeltoid bursitis and bicipital tendinitis) in adult patients. In this double-blind (double-dummy), randomised, parallel group study over two weeks, 122 patients were included. The Mann-Whitney statistics revealed therapeutic equivalence of both treatments with a slight superiority for nimesulide. The tolerability of nimesulide, judged by investigators and patients and analysed statistically, was superior to that of diclofenac. Thus, the benefit-risk relationship was better for the test drug than for the reference drug.

Adolescent↗