Expert opinion on drug metabolism & toxicology
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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.
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Expert Opin Drug Metab Toxicol · Jan 2008
ReviewRole of pharmacogenetics in variable response to drugs: focus on opioids.
Pharmacogenetics is the study of the role of genetics in inter-individual variability to drug response and therapy. This review provides a comprehensive report of the present status of pharmacogenetic studies for opioid drugs. Opioid analgesics are widely used clinically for pain management, and inter-patient variability with opioid therapy is often reported. ⋯ Pharmacogenetics of enzymes, including the cytochrome P450s and uridine diphosphoglucuronosyltransferases, opioid receptors and the ABC family of transporters, is reviewed. The role of genetic variability in clinical opioid therapy is examined, and relevant clinical trials cited. The present status of opioid pharmacogenetics, promises and challenges and future directions are discussed.
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Expert Opin Drug Metab Toxicol · Oct 2007
ReviewThe role of oseltamivir in the treatment and prevention of influenza in children.
The burden of seasonal influenza in children is poorly recognized, in spite of the potential for severe and even life-threatening illness and common secondary complications. Children are a primary reservoir for the spread of influenza to both family members and the community, which imposes a sizeable social and economic strain. Although vaccination is the primary intervention against childhood influenza, the antiviral neuraminidase inhibitors, oseltamivir and zanamivir, provide treatment options. ⋯ Oseltamivir has shown excellent tolerability and a low potential for viral resistance in pediatric studies. In the event of an influenza pandemic, oseltamivir is expected to be at the forefront of containment strategies. This article reviews the pharmacology, efficacy and tolerability of oseltamivir as treatment and prophylaxis in children.
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Expert Opin Drug Metab Toxicol · Aug 2006
ReviewTadalafil for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.
This article reviews the pharmacological properties of tadalafil and the current evidence supporting its use for treating symptomatic benign prostatic hyperplasia (BPH). The rationale for using tadalafil for BPH stems from the following three observations: first, the prevalence of lower urinary tract symptoms (LUTS), BPH and erectile dysfunction (ED) increases with age; second, phosphodiesterase-5 (PDE5) inhibition mediates smooth muscle relaxation in the lower urinary tract; and third, early clinical evidence demonstrates that PDE5 inhibitors such as tadalafil are successful in treating LUTS and ED. ⋯ The ability to treat both BPH and ED with one medication is noteworthy given the significant negative impact in quality-of-life measures these disorders have in ageing men. Careful patient selection and further trials are warranted.