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Biomedical subjects

Lesley J Scott

Publications and source records attributed to Lesley J Scott.

At least 19 recordsLinked to original sources
PubMed2007

Fixed-dose combination lercanidipine/enalapril.

Lercanidipine, a dihydropyridine calcium channel blocker, and enalapril, an ACE inhibitor, are established antihypertensive agents. A fixed-dose tablet formulation of lercanidipine/enalapril is approved in Germany for the treatment of hypertension in patients not responding to monotherapy. Lercanidipine/enalapril 10mg/10mg once daily significantly reduced sitting diastolic blood pressure and sitting systolic blood pressure, relative to lercanidipine 10mg once daily, in a 12-week, randomised, double-blind trial in patients with mild to moderate hypertension who had previously not responded to 4 weeks' treatment with lercanidipine. In a similarly designed trial, lercanidipine/enalapril 10mg/20mg once daily was significantly more effective than enalapril 20mg once daily in hypertensive patients who had previously not responded to enalapril monotherapy. Fixed-dose lercanidipine/enalapril was generally well tolerated, with a tolerability profile similar to that of either of the individual drugs alone or placebo. Cough was reported in <or=5.2% and peripheral oedema in <or=1.5% of lercanidipine/enalapril recipients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Telmisartan: a review of its use in the management of hypertension.

Telmisartan (Micardis, Pritor), a highly selective angiotensin II (AII) type 1 (AT1) receptor antagonist, is approved for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents. The long elimination half-life of telmisartan ensures the drug provides effective reductions in blood pressure (BP) across the entire 24-hour dosage interval. Extensive evidence from well designed clinical trials and the clinical practice setting indicates that telmisartan, either as monotherapy or in combination with other antihypertensive agents, provides long-term antihypertensive efficacy and is well tolerated in a broad spectrum of hypertensive patients, including the elderly and those with coexisting type 2 diabetes mellitus, metabolic syndrome and/or renal impairment. Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 6 hours of this period. Independent of its effect on BP, telmisartan displays favourable effects on insulin resistance, lipid levels, left ventricular hypertrophy (LVH) and renal function. The consistent antihypertensive efficacy during the entire 24-hour dosage interval and sustained BP-lowering effect in the long term, combined with its favourable tolerability profile, mean that telmisartan is a valuable first-line treatment option for the management of essential hypertension.

Antihypertensive Agents↗
PubMed2006

Letrozole : in postmenopausal hormone-responsive early-stage breast cancer.

Letrozole is a highly selective, nonsteroidal, third-generation aromatase inhibitor approved for first-line and extended adjuvant therapy in postmenopausal women with hormone-responsive, early-stage breast cancer. Binding of letrozole to the haeme component of the cytochrome P450 subunit of aromatase inhibits estrogen biosynthesis throughout the body. As first-line adjuvant therapy in approximate, equals 8000 postmenopausal women with hormone-responsive, early-stage breast cancer, once-daily letrozole 2.5mg significantly prolonged disease-free survival (DFS; primary endpoint) and reduced the risk of relapse at distant sites relative to once-daily tamoxifen 20mg in the ongoing Breast International Group 1-98, double-blind, multinational trial. The median duration of follow-up for this primary core analysis was 25.8 months. Extended adjuvant therapy with once-daily letrozole 2.5mg significantly prolonged DFS relative to placebo treatment at a median follow-up of 30 months (primary endpoint) in the MA-17 trial in approximate, equals 5000 postmenopausal women who were disease free after 4.5-6 years of tamoxifen therapy for hormone-responsive, early-stage breast cancer. Letrozole treatment for up to 5 years was generally well tolerated in this clinical setting. As first-line treatment, relative to tamoxifen, letrozole was associated with a significantly lower incidence of venous thromboembolitic events, vaginal bleeding, hot flushes and night sweating, whereas the incidence of cardiac failure, bone fractures and arthralgia was higher in letrozole recipients.

Adult↗
PubMed2006

Levocetirizine: a review of its use in the management of allergic rhinitis and skin allergies.

Levocetirizine (Xyzal) is a selective, potent, oral histamine H(1) receptor antagonist of the latest generation that is licensed for the symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis [PER]) and chronic idiopathic urticaria (CIU). Large, well designed trials indicate that levocetirizine is effective and generally well tolerated in the treatment of allergic rhinitis and CIU. Its pharmacological profile offers many positive aspects: a rapid onset and long duration of antihistaminic effect; rapid absorption and high bioavailability; a low potential for drug interactions; a low volume of distribution; and a lack of effect on cognition, psychomotor function and the cardiovascular system. Allergen challenge chamber studies suggest that levocetirizine has better efficacy than desloratadine, loratadine or fexofenadine. Well controlled, long-term studies with other later-generation H(1) receptor antagonists are required to fully define its clinical profile relative to other agents in this class. Overall, levocetirizine is a valuable addition to the oral H(1) receptor antagonists available for the treatment of allergic rhinitis and as first-line therapy in patients with CIU.

Cetirizine↗
PubMed2006

Methylphenidate transdermal system: In attention-deficit hyperactivity disorder in children.

The methylphenidate transdermal system (MTS) patch is approved by the US FDA for use in children aged 6-12 years with attention-deficit hyperactivity disorder (ADHD). This delivery system permits sustained absorption of the drug through the skin and into the bloodstream. Methylphenidate (MPH) is a CNS agent thought to act on dopamine and noradrenaline (norepinephrine) pathways and thereby blocks the reuptake of these neurotransmitters into the presynaptic neuron. In children with ADHD, MTS patches releasing MPH doses of 10-30 mg over a 9-hour period (12.5-37.5 cm2 patch size) is steadily absorbed, with mean peak plasma concentrations of d-MPH (20-46.5 ng/mL) reached in approximately 8 hours. In well controlled trials in children with ADHD, patients administered MTS patches releasing MPH 10-30 mg over approximately 9 hours showed significantly greater improvements in their ADHD symptoms than placebo recipients. MTS patches are generally well tolerated in paediatric patients with ADHD, with treatment-emergent events being similar in nature to those reported with oral MPH. The majority of adverse events were mild to moderate in intensity.

Administration, Cutaneous↗
PubMed2006

Adalimumab: in psoriatic arthritis.

Adalimumab, a fully human monoclonal antibody, is a tumour necrosis factor antagonist that has been investigated for efficacy in psoriatic arthritis, based on well-established use of the drug in rheumatoid arthritis. In well-controlled Phase III trials, adalimumab (40 mg administered subcutaneously every other week) has shown efficacy in adult patients with psoriatic arthritis who had an inadequate response to previous treatment with NSAIDs (24-week ADEPT trial; n = 313) or disease-modifying antirheumatic drugs (12-week study; n = 100). In these trials, adalimumab recipients experienced a significantly greater improvement in arthritis response (p < 0.001 in the ADEPT trial, and p <or= 0.05 in the smaller study) than placebo recipients, as assessed by the ACR20, ACR50 and ACR70 response rates. There was radiographic evidence of progressive joint damage in the placebo group but not the adalimumab group at 24 weeks in the ADEPT trial, according to the mean total Sharp score modified for psoriatic arthritis. The signs and symptoms of psoriasis in patients with psoriatic arthritis were clinically and statistically more improved with adalimumab than with placebo, according to the PASI responses, at 12 and 24 weeks in the ADEPT trial (e.g. PASI50 rate 75% vs 12% at 24 weeks; p < 0.001). Adalimumab was generally well-tolerated in clinical trials of psoriatic arthritis; the adverse event profile appears to be similar to that associated with use of the drug in rheumatoid arthritis.

Adalimumab↗
PubMed2006

Intravenous ibandronate: in the treatment of osteoporosis.

Ibandronate (ibandronic acid) is a potent nitrogen-containing bisphosphonate that inhibits osteoclast-mediated bone resorption in women with postmenopausal osteoporosis. Recently, an intravenous (IV) formulation of ibandronate for intermittent injection, which circumvents the fasting and posture requirements associated with administration of oral bisphosphonates, was approved for use in this patient population. In initial placebo-controlled studies of 1 year's duration, IV ibandronate (< or =2mg once every 3 months) increased lumbar spine bone mineral density (BMD) and reduced levels of biochemical markers of bone turnover in a dose-dependent manner. Dosages < or =1mg every 3 months were found to be suboptimal in terms of fracture prevention in a 3-year trial. Subsequently, the large randomised, double-blind, noninferiority DIVA trial showed that, in terms of increasing lumbar spine BMD (primary endpoint), IV ibandronate 3mg once every 3 months and 2mg once every 2 months for 1 year were noninferior and also superior to oral ibandronate 2.5mg once daily, a regimen with proven antifracture efficacy. Median reductions from baseline in biochemical markers of bone turnover were similar for the IV and oral regimens. IV ibandronate was generally well tolerated in clinical trials. Treatment-related adverse events included musculoskeletal events and transient influenza-like symptoms, the latter mainly associated with the first dose.

Animals↗
PubMed2006

Entecavir: a review of its use in chronic hepatitis B.

Entecavir (Baraclude) is a novel nucleoside analogue of 2'-deoxyguanosine whose intracellular triphosphate form inhibits replication of the hepatitis B virus (HBV). In large, randomised, double-blind, phase III clinical trials in patients with chronic HBV infection, oral entecavir 0.5 or 1.0mg once daily for up to 96 weeks was superior to lamivudine 100 mg/day in improving hepatic histology, normalising aminotransferase levels and suppressing viraemia to levels undetectable by polymerase chain reaction (PCR) assay in nucleoside-naive hepatitis B e antigen (HBeAg)-negative (precore or core promoter mutants) and/or HBeAg-positive patients, and in lamivudine-refractory (persistent viraemia during lamivudine therapy) HBeAg-positive patients. In addition, the tolerability profile of entecavir was generally similar to that of lamivudine. Thus, entecavir is a primary option in the treatment of chronic HBV infection in both nucleoside-naive and lamivudine-refractory patients.

Adolescent↗
PubMed2006

Pioglitazone/metformin.

A fixed-dose pioglitazone/metformin tablet is approved in the US and the EU for the treatment of adult patients with type 2 diabetes mellitus who currently have inadequate glycaemic control with metformin monotherapy. In the US, the combination tablet is also approved for the treatment of adult patients with type 2 diabetes who currently have inadequate glycaemic control with pioglitazone monotherapy and for those already receiving a combination of pioglitazone and metformin. Bioequivalence, based on absorption and bioavailability parameters, has been established between the fixed-dose tablets and equivalent doses of pioglitazone and metformin coadministered as separate agents. Combination therapy with pioglitazone plus metformin was significantly more effective at improving both glycaemic and lipid control than metformin plus placebo in patients with type 2 diabetes in a 16-week, well designed trial. Pioglitazone plus metformin demonstrated similar antihyperglycaemic efficacy to that of rosiglitazone plus metformin in a well designed 12-month trial; however, pioglitazone plus metformin was the superior combination in terms of lipid control. In several comparative trials of 1-3.5 years' duration, pioglitazone plus metformin was at least as effective as combination therapy with a sulphonylurea plus metformin in terms of antihyperglycaemic efficacy, but provided superior lipidaemic control with regard to levels of triglyceride and high-density lipoprotein-cholesterol. Pioglitazone plus metformin was generally well tolerated in patients with type 2 diabetes, with adverse events common to metformin monotherapy observed at a similar incidence to that with metformin plus placebo.

Diabetes Mellitus, Type 2↗
PubMed2006

Recombinant full-length parathyroid hormone (1-84).

Full-length parathyroid hormone (PTH) 1-84 is a recombinant version of human PTH. It is approved in the EU for the treatment of postmenopausal women with osteoporosis who have a high risk of fractures. Once-daily subcutaneous administration of PTH(1-84) stimulates new bone formation and increases bone mass. In the pivotal, randomised, double-blind, multicentre, 18-month TOP trial in 2532 postmenopausal women with osteoporosis, subcutaneous PTH(1-84) 100 microg/day significantly reduced the incidence of new or worsened vertebral fractures relative to placebo (primary endpoint). Moreover, the increase from baseline in bone mineral density (BMD) at the lumbar spine, total hip, femoral neck and trochanter was also significantly greater than in the placebo group. In another well designed study (PaTH; n = 238), 1 year of subcutaneous PTH(1-84) 100 microg/day followed by 1 year of alendronate 10 mg/day resulted in significantly greater increases in total spine, femoral neck and total hip BMD at 24 months compared with patients who received placebo for the second year. During the first year, PTH(1-84) in combination with alendronate was no more effective than PTH(1-84) monotherapy in terms of increasing areal lumbar spine BMD. PTH(1-84) is generally well tolerated, although patients should be monitored for elevated serum calcium.

Animals↗
PubMed2006

Retigabine: in partial seizures.

Retigabine has anticonvulsant properties that appear to be primarily mediated by opening neuronal voltage-gated potassium channels. This action has been shown in neuronal KCNQ2/3 and KCNQ3/5 potassium channels. In addition to this unique action, retigabine also potentiates GABA-evoked currents in cortical neurons at high concentrations. When used as adjunctive therapy in patients with partial seizures, retigabine 600-1200 mg/day (200-400 mg three times daily) was associated with significant linear dose-dependent reductions in monthly seizure frequency compared with placebo in a large 16-week randomised phase II trial. Median monthly seizure frequency decreased from baseline by up to 35% among patients in the retigabine treatment arms compared with 13% in the placebo group. Retigabine 1200 mg/day was also significantly more effective than retigabine 600 mg/day. Responder rates, defined as the proportion of patients with > or = 50% reduction in seizure frequency, were significantly higher among patients in the retigabine 900 and 1200 mg/day groups than in those who received placebo. CNS-related adverse events were the most commonly reported treatment-emergent adverse events associated with retigabine in clinical trials. Across all three retigabine groups in the large phase II trial, somnolence (20.3%), dizziness (14.6%), confusion (12.3%) and speech disorder (11.3%) were the most frequent CNS-related adverse events.

Animals↗
PubMed2006

Rufinamide.

Rufinamide, a triazole derivative, reduces the recovery capacity of neuronal sodium channels after inactivation, limiting neuronal sodium-dependent action potential firing and mediating anticonvulsant effects. In children, adolescents and adults, adjunctive oral rufinamide was more effective than placebo in treating seizures associated with treatment-resistant Lennox-Gastaut syndrome in a well designed 16-week trial. Rufinamide recipients experienced significantly greater reductions from baseline than placebo recipients in the median frequency of total seizures and tonic-atonic seizures per 28 days and demonstrated improvements in seizure severity. Furthermore, these beneficial effects of rufinamide on seizure frequency were maintained throughout a subsequent 3-year, open-label extension study. Relative to placebo, adjunctive rufinamide significantly reduced the frequency of partial seizures per 28 days in adult patients with inadequately controlled partial seizures in two well designed trials of approximate, equals3 months duration, with a higher proportion of rufinamide recipients achieving a reduction of >or=50% in partial seizure frequency per 28 days. Rufinamide was generally well tolerated in patients with Lennox-Gastaut syndrome and in those with partial seizures, with adverse events being mostly mild or moderate in severity.

Animals↗
PubMed2006

Escitalopram: a review of its use in the management of anxiety disorders.

Escitalopram (Cipralex, Lexapro, Seroplex, Sipralexa), the therapeutically active S-enantiomer of racemic citalopram (RS-citalopram), is a potent and highly selective serotonin reuptake inhibitor. It is effective and generally well tolerated in the treatment of moderate to severe generalised anxiety disorder (GAD) or social anxiety disorder (SAD), panic disorder (with or without agoraphobia) as well as obsessive-compulsive disorder (OCD). Moreover, escitalopram is at least as effective as paroxetine for the treatment of GAD, SAD or OCD and appears to achieve a more rapid response than racemic citalopram in the management of panic disorder. Generally, it has a more favourable tolerability profile than paroxetine in terms of fewer discontinuation symptoms. In addition, a favourable pharmacokinetic profile permits once-daily administration of the drug. Additional comparative studies are required to definitively position escitalopram with respect to other SSRIs and venlafaxine. Nevertheless, available clinical data indicate that escitalopram is an effective first-line treatment option for the management of GAD, SAD, panic disorder and OCD.

Animals↗
PubMed2006

Ziprasidone: a review of its use in schizophrenia and schizoaffective disorder.

Ziprasidone (Geodon, Zeldox) is an atypical antipsychotic agent with a unique neurotransmitter receptor-binding profile. The oral formulation is indicated for the treatment of adult patients with schizophrenia and the intramuscular formulation for the control of acute agitation in these patients. In adult patients with schizophrenia or schizoaffective disorder, oral ziprasidone was effective at a dosage of 40-80 mg twice daily in patients experiencing a phase of acute illness, and at a dosage of 20-80 mg twice daily in those with chronic schizophrenia or schizoaffective disorder, including those who were symptomatically stable. Ziprasidone offers the advantage over most other atypical antipsychotic agents of being available in a fast-acting intramuscular formulation for control of acute agitation, thus providing clinicians with the option to safely and effectively transition to longer-term treatment with the oral formulation. Although careful consideration should be given to the propensity for ziprasidone to cause corrected QT (QTc) interval prolongation, albeit at a relatively low incidence, the drug generally has a favourable tolerability profile of low extrapyramidal syndrome (EPS) liability, neutral bodyweight gain, and potentially low propensity for metabolic complications. Thus, ziprasidone is an effective option for the management of patients with schizophrenia or schizoaffective disorder, with the intramuscular formulation providing a useful option for the treatment of acute agitation in these patients.

Antipsychotic Agents↗
PubMed2006

Spotlight on infliximab in Crohn disease and rheumatoid arthritis.

Infliximab (Remicade) is a chimeric monoclonal antibody against tumor necrosis factor (TNF)-alpha that has shown efficacy in Crohn disease and rheumatoid arthritis with a disease-modifying activity and rapid onset of action. It is administered intravenously, generally in a schedule with initial infusions at 0, 2, and 6 weeks, followed by administration once every 8 weeks. Infliximab is effective in the treatment of patients with moderately to severely active Crohn disease with an inadequate response to other treatment options or those with fistulizing disease. In combination with methotrexate, infliximab reduced signs and symptoms and delayed disease progression in patients with active, methotrexate-refractory rheumatoid arthritis and in those with early disease. The drug was generally well tolerated. Recrudescence of tuberculosis infection and worsening of heart failure and demyelinating disease are among some of the concerns with anti-TNFalpha therapy, requiring cautious use of these agents in high-risk patients. Current data suggest that infliximab may be cost effective, especially when long-term clinical outcomes and burden of the diseases are taken into account. More robust, prospective pharmacoeconomic studies are required to better ascertain the cost effectiveness of infliximab. Direct head-to-head comparative trials of infliximab with other biological agents are not yet available and would be helpful in determining with greater certainty the place of infliximab in the management of these diseases. Nonetheless, infliximab, like other biological agents, is a valuable treatment option in patients with moderately to severely active Crohn disease (including fistulizing disease) or rheumatoid arthritis (including early disease).

Antibodies, Monoclonal↗
PubMed2006

Adalimumab: a review of its use in adult patients with rheumatoid arthritis.

Adalimumab (Humira) is a recombinant, fully human anti-tumor necrosis factor (TNF) monoclonal antibody approved in the US and Europe for the treatment of adult patients with moderate to severe, active rheumatoid arthritis (RA). In combination with methotrexate or standard antirheumatic therapy or as monotherapy, adalimumab effectively reduced signs and symptoms of RA, induced remission, improved physical function and inhibited the progression of structural damage in several randomized, double-blind, placebo-controlled phase III trials. The drug was generally well tolerated, with most adverse events being mild to moderate, and the serious adverse events profile being similar to that generally seen in patients with RA not receiving anti-TNF agents. Adalimumab was at least as cost effective as other anti-TNF agents used in the therapy of RA, and provided significant improvements in patients' health-related quality of life. Overall, adalimumab in combination with methotrexate or standard antirheumatic therapy is valuable as a first-line therapeutic option in patients with early, aggressive RA, and a second-line therapeutic option in patients with long-standing, moderate to severe RA. For the latter indication, adalimumab may also be used as monotherapy.

Adalimumab↗
PubMed2006

Reteplase: a review of its use in the management of thrombotic occlusive disorders.

Reteplase (Retavase) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific). Reteplase can be administered as a bolus dose (nonweight-based) rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival. In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke. Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other thrombolytic agents. With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.

Arterial Occlusive Diseases↗