Expert opinion on drug metabolism & toxicology
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Restless legs syndrome (RLS) is a chronic neurological disorder associated with sleep disturbance. Ropinirole, a non-ergot dopamine agonist, has been widely studied for the treatment of moderate-to-severe primary RLS in a comprehensive clinical development program. In these studies, ropinirole was effective in significantly improving the symptoms of RLS, compared with placebo, in patients with moderate-to-severe primary RLS. ⋯ Significant improvements in RLS symptoms were observed within 2 nights of treatment. Ropinirole also produced significant benefits on objective measures of RLS motor symptoms, such as periodic leg movements; and on subjective measures of sleep, ropinirole was generally well tolerated. A newly developed extended-release formulation of ropinirole may benefit patients who warrant an extended duration of therapy.
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Dexmedetomidine is an alpha-2 adrenoreceptor agonist with sedative, analgesic and anxiolytic properties. Since its release in the US market in late 1999, it has gained remarkable attention in the adult, pediatric and geriatric populations, predominantly because of its minimal respiratory depression. However, beyond its well-known properties, dexmedetomidine has recently been investigated for its potential in many other clinical scenarios, including neuroprotection, cardioprotection and renoprotection, with promising results. ⋯ Dexmedetomidine is a novel agent with a wide safety margin and excellent sedative and moderate analgesic properties. Though its broadest use is currently in surgical and nonsurgical intensive care unit patients, dexmedetomidine appears to have promising future applications in the areas of neuroprotection, cardioprotection and renoprotection.
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Expert Opin Drug Metab Toxicol · May 2008
ReviewPharmacokinetic/pharmacodynamic modeling of cardiac toxicity in human acute overdoses: utility and limitations.
Hypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings. ⋯ A sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.
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Expert Opin Drug Metab Toxicol · May 2008
ReviewSertindole: pharmacological and clinical profile and role in the treatment of schizophrenia.
Sertindole is a second-generation antipsychotic recently reintroduced in the market for the treatment of schizophrenia after a reevaluation of its risks and benefits. ⋯ Findings from controlled clinical trials have demonstrated that sertindole is at least as effective as haloperidol and risperidone against the positive symptoms of schizophrenia, while it appears superior against negative symptoms. Preliminary evidence suggests that sertindole has beneficial effects on cognitive function. Sertindole is associated with a low rate of extrapyramidal side effects, lacks sedative properties, and may induce a moderate weight gain. No clinically relevant elevations in serum prolactin, glucose or lipid levels have been so far documented in sertindole-treated patients. On the other hand, administration of sertindole may result in a prolongation of the QTc interval, with subsequent risk of serious arrhythmias. However, postmarketing surveillance studies have recently indicated that sertindole is not associated with a higher rate of cardiovascular mortality than other antipsychotic agents.