Nimodipine in subcortical vascular dementia trial.

Vascular dementia (VaD) is a heterogeneous pathology currently regarded as the result of a variety of causes. Different types of VaD can be identified according to different criteria. This heterogeneity might be one of the causes of the controversial results observed, up to now, in clinical trials. Recently, the 10th revision of the International Classification of Diseases (ICD-10) explicitly identified subcortical VaD as a well-defined subgroup. Abnormalities of white matter are clearly detectable with computed tomography or magnetic resonance scans. The clinicoradiological association of dementia, blood hypertension, and other vascular risk factors, extensive white matter lesions, and small subcortical infarcts might be considered as a clinical univocal entity. Following the encouraging results of a preliminary pilot study, the above-mentioned criteria were followed to define a population of patients to be enrolled in a double-blind, parallel-groups, placebo-controlled clinical trial with nimodipine, which has been proposed as a drug that can improve cognitive functions in patients with VaD. The paper discusses the protocol design of this ongoing trial and its main entry criteria, with particular emphasis on the definition of the population to be enrolled. Implication for future trials in subcortical VaD are discussed further.

Tolerability and pharmacokinetics of ebrotidine in healthy subjects given single and repeated oral doses.

The tolerability and safety of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl] thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) and its basic pharmacokinetic parameters were determined after its oral administration to healthy volunteers. Sixteen subjects were selected to participate in two different studies: an increasing single dose study to determine the maximal tolerated dose (from 25 to 1600 mg), and a multiple dose study (stepped doses from 400 to 1600 mg daily for 12 days). The results of the studies showed that ebrotidine has a good tolerability. Vital signs and laboratory tests were not influenced by the study treatment. No clinically relevant adverse effects were reported during the investigation. Ebrotidine reached peak plasma concentrations 2-3 h after oral administration. Its elimination half-life ranged from 9 to 14 h. In conclusion, ebrotidine was well tolerated after administration of oral single doses of up to 1600 mg, and after repeated administration of up to 800 mg/12 h for 12 days.

Pharmacokinetics and tolerance of sertaconazole in man after repeated percutaneous administration.

The local and systemic tolerance of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H- imidazol-1-yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) 2% cream was studied in healthy volunteers after cutaneous application in an increasing-dose schedule during 13 days. Blood and urine samples were collected after the application of 16 g of cream. Percentage of absorption was determined in eight 3 x 3 cm areas of the volar arm skin after 2 mg cream topical application. No changes on vital signs (blood pressure, heart rate and body temperature) or in the ECG were found during the trial. Sertaconazole did not produce skin irritation nor systemic side effects. Sertaconazole was not detected in either the serum and urine samples obtained. The percentage of cutaneous absorption at 24 h after administration reached 72% of the applied dose.

[Treatment of acute pain in a general hospital: opinions of physicians and nurses]. / Tratamiento del dolor agudo en un hospital general: opiniones de médicos y enfermeras.

A survey was carried amongst physicians and nurses of a general hospital, in order to know their opinion about acute pain treatment. Out of 106 physicians and 153 nurses questioned, 72 and 105 respectively answered the questionnaire. Two thirds of them though that analgesic treatment was currently good, although, it could be improved if they increased their knowledge about it. Twenty nine per cent of physicians thought that their patients were receiving lower doses than what they had prescribed and that this fact could be responsible for the treatment failure. Those questioned believed that approximately 30% of patients treated with opium derivatives for over a week could develop addiction problems. Our study confirmed the existence of inadequate attitudes towards the need for analgesics in patients with acute pain.

Effect of quinolones on caffeine disposition.

Six healthy volunteers received a single caffeine dose after pretreatment with norfloxacin, pipemidic acid, or placebo in a crossover, randomized, single-blind clinical trial. Quinolones altered the pharmacokinetics of caffeine, with a significant increase in the AUCs and a decrease in plasma clearance. The elimination half-life increased significantly with pipemidic acid. The apparent volume of distribution, mean renal clearance, and time to reach maximum caffeine concentrations remained unaltered. There was a decline in caffeine metabolite levels in the 24-hour urine samples for both quinolone treatments, suggesting that pipemidic acid and, to a lesser degree, norfloxacin inhibit metabolism of the N-demethylation pathways of caffeine. The practical consequence of this observation could be caffeine accumulation during repeated intake of coffee. In two additional healthy volunteers under a controlled multiple-dose regimen of caffeine ingestion, administration of pipemidic acid for 2 days caused a fourfold increase in the plasma concentrations of caffeine.

Diclofenac versus dipyrone in acute renal colic: a double-blind controlled trial.

A randomized, double-blind clinical trial in 50 patients was done to compare the efficacy and tolerance of single doses of intramuscular diclofenac 75 mg and dipyrone 2 g in acute renal colic. Both drugs were equally effective, but diclofenac was better in terms of complete relief of pain. Vital signs were affected according to the stress and pain.