British journal of clinical pharmacology
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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.
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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 · Sep 2004
Randomized Controlled Trial Clinical TrialCan coadministration of oxycodone and morphine produce analgesic synergy in humans? An experimental cold pain study.
The coadministration of subantinociceptive doses of oxycodone with morphine has recently been shown to result in a synergistic antinociceptive effect in rats. The present study was aimed to investigate the possibility that coadministration of morphine and oxycodone can produce a similar synergistic effect in humans exposed to an experimental model of cold pressor test (CPT). ⋯ These results indicate that at the doses tested, morphine and oxycodone do not produce synergistic antinociceptive effects in healthy humans exposed to the CPT.
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Br J Clin Pharmacol · Sep 2004
Vancomycin pharmacokinetics in critically ill patients receiving continuous venovenous haemodiafiltration.
To investigate the pharmacokinetics of vancomycin in critically ill patients on continuous venovenous haemodiafiltration (CVVHDF), a continuous renal replacement therapy (CRRT) and to see if routine measures approximate vancomycin clearance. ⋯ Vancomycin is cleared effectively by CVVHDF. Clearance was faster than other forms of CRRT, therefore doses need to be relatively high. Urea clearance slightly overestimates vancomycin clearance. The administered doses of 750 mg every 12 h were too high and accumulation occurred, as only approximately 60% of a dose was cleared over this period. The maintenance dose required to achieve a target average steady-state plasma concentration of 15 mg l(-1) can be calculated as 450 mg every 12 h.