British journal of clinical pharmacology
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Br J Clin Pharmacol · Nov 2004
Randomized Controlled Trial Clinical TrialConcurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses.
The use of acetylcholinesterase inhibitors for the treatment of comorbid Alzheimer's disease in Parkinson's disease (PD) patients stabilized on a levodopa regimen may potentially disrupt cholinergic balance. This randomized, double-blind, crossover study investigated the safety of, and possible drug-drug interaction between, donepezil HCl and levodopa/carbidopa. ⋯ No clinically significant drug-drug interactions between donepezil HCl and levodopa/carbidopa were observed at steady state. The small changes in the pharmacokinetics of levodopa did not result in any change in motor symptoms. Co-administration of the two drugs led to a small increase in adverse events compared with administration of levodopa/carbidopa alone in PD patients. These adverse events, however, were consistent with donepezil's cholinomimetic effect, and their incidence was comparable to that observed following the administration of donepezil HCl alone.
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Br J Clin Pharmacol · Nov 2004
Randomized Controlled Trial Comparative Study Clinical TrialA randomized, double-blind, placebo controlled trial of melatonin add-on therapy in epileptic children on valproate monotherapy: effect on glutathione peroxidase and glutathione reductase enzymes.
To compare the effect of add-on melatonin with placebo on the antioxidant enzymes (glutathione peroxidase and glutathione reductase) in epileptic children on valproate monotherapy. ⋯ Melatonin exerts neuroprotection due to its antioxidant, antiexcitotoxic and free radical scavenging properties within the central nervous system. Melatonin, thus, as an adjunct, can be a putative neuroprotector in conditions involving oxidative stress like epilepsies.
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Br J Clin Pharmacol · Nov 2004
ReviewThe safety and tolerability of donepezil in patients with Alzheimer's disease.
Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine, have been approved for the symptomatic treatment of Alzheimer's disease (AD) for over a decade. However, the first ChE inhibitors were associated with a high incidence of side-effects and general tolerability concerns, including hepatotoxicity. Side-effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. ⋯ The incidence of weight loss is very similar between donepezil- and placebo-treated patients. Although insomnia and other sleep disorders have been reported following administration of donepezil, lengthening the time period before increasing the dose of donepezil from 5 to 10 mg day(-1) or switching to morning dosing can reduce these events to the levels of placebo-treated patients. Over 770 million days of patient use and an extensive publication database demonstrate that donepezil has a good tolerability and safety profile.
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Br J Clin Pharmacol · Nov 2004
Clinical Trial Controlled Clinical TrialConcurrent administration of donepezil HCl and risperidone in patients with schizophrenia: assessment of pharmacokinetic changes and safety following multiple oral doses.
This open-label, multiple-dose trial investigated the effect of concurrent administration of donepezil HCl with risperidone on the pharmacokinetics (PK) and safety profiles of both drugs. ⋯ These results suggest that once-daily dosing of 5 mg donepezil HCl does not alter the PK of risperidone in patients with schizophrenia. The combination of risperidone and donepezil HCl was well tolerated.