ABSTRACT
Treatment with neurotrophic agents might enhance and/or prolong the effects of cholinesterase inhibitors (ChEIs) in Alzheimer's disease (AD). We compared the safety and efficacy of the neurotrophic compound Cerebrolysin (10 ml; n=64), donepezil (10 mg; n=66) and a combination of both treatments (n=67) in mild-to-moderate (mini-mental state examination-MMSE score 12-25) probable AD patients enrolled in a randomized, double-blind trial. Primary endpoints were global outcome (Clinician's Interview-Based Impression of Change plus caregiver input; CIBIC+) and cognition (change from baseline in AD Assessment Scale-cognitive subscale+; ADAS-cog+) at week 28. Changes in functioning (AD Cooperative Study-Activities of Daily Living scale, ADCS-ADL) and behaviour (Neuropsychiatric Inventory, NPI) were secondary endpoints. Treatment effects in cognitive, functional and behavioral domains showed no significant group differences; whereas improvements in global outcome favored Cerebrolysin and the combination therapy. Cognitive performance improved in all treatment groups (mean±SD for Cerebrolysin: -1.7±7.5; donepezil: -1.2±6.1; combination: -2.3±6.0) with best scores in the combined therapy group at all study visits. Cerebrolysin was as effective as donepezil, and the combination of neurotrophic (Cerebrolysin) and cholinergic (donepezil) treatment was safe in mild-to-moderate AD. The convenience of exploring long-term synergistic effects of this combined therapy is suggested.
Subject(s)
Alzheimer Disease/drug therapy , Amino Acids/administration & dosage , Indans/administration & dosage , Neuroprotective Agents/administration & dosage , Piperidines/administration & dosage , Activities of Daily Living , Aged , Donepezil , Double-Blind Method , Female , Humans , Male , Neuropsychological Tests , Treatment OutcomeABSTRACT
The objective of the meta-analysis was to assess the efficacy and safety of a single oral dose of 800 mg pefloxacin in the treatment of acute uncomplicated lower urinary tract infections in women. A total of 1578 women were enrolled in five controlled (four double-blind and one open) and two non-comparative multicentre clinical trials. The comparative treatment regimen in the five controlled trials was trimethoprim-sulfamethoxazole in four studies, and norfloxacin in one study. Trimethoprim-sulfamethoxazole was administered orally 160/800 mg twice daily for 3-7 days, norfloxacin 400 mg b.i.d. for 5 days. Analyses of these studies were performed for the intent-to-treat population and safety population. The 1298 patients (815 patients with pefloxacin, 404 with trimethoprim-sulfamethoxazole, and 79 with norfloxacin) included in the intent-to-treat-analysis were those with clinical signs and symptoms of acute cystitis and significant bacteriuria (>/=10(5) cfu/ml midstream urine) who received a single oral dose of pefloxacin or were treated with the control drug. Success rates of pefloxacin achieved 4 to 6 weeks after the start of treatment ranged from 65.8% to 97.7% for cure or improvement of clinical signs and symptoms and from 53.8% to 90.5% for bacteriological eradication (trimethoprim-sulfamethoxazole 69.1% to 92.5% abd 52.1% to 85.1%, and norfloxacin 74.7% and 58.2%, respectively). The pooled percentage of patients in whom pefloxacin therapy cured or improved clinical symptoms was 82.5% (95% CI: 79.7% to 85.0%). The pooled rate of bacteriological eradication was 76.3% (95% CI: 73.2% to 79.2%). The pooled success rates of trimethoprim-sulfamethoxazole were 82.7% (95% CI: 78.6% to 86.2%) for clinical cure or improvement, and 74.3% (95% CI: 69.7% to 78.5%) for bacteriological eradication. Testing for equivalence between pefloxacin and trimethoprim-sulfamethoxazole in an exploratory sense, the minimal equivalence region with significant results was 4.1% points for clinical cure or improvement (P < 0.05) and 6.5% points for bacteriological eradication (P < 0.05). Adverse events were reported in 235 out of 987 patients treated with pefloxacin. The pooled incidence was 23.8% (incidence in individual studies 13.5% to 47.3%). The pooled incidence of adverse events associated with the use of the comparative drugs was 20.5% (incidence in individual studies 5.9 to 47.7%).
ABSTRACT
Pharmacokinetic Variables under Therapy with a Nonsteroidal Antirheumatic with a Short Half-life Measured in 65-80 Years Old Patients. The pharmacokinetic variables of ibuprofen (Ibuprofen Klinge 600) (terminal half-life, cmax, tmax, area under the curve) have been measured in 65-80 years old patients with rheumatic diseases, to investigate the tolerance under the aspect of cumulating effects in the serum level concentration of ibuprofen in these patients with impaired renal function caused by their old age. The results show that there is no clinically significant deviation of the values compared with published data in younger patients. There was no increase in half-life and cmax. Therefore ibuprofen can be used in old patients with rheumatic diseases without any dose reduction and discontinuation of treatment has not to be discussed.
