Amiodarone concentrations in plasma and fat tissue during chronic treatment and related toxicity.

Aims: To determine if amiodarone, highly lipophilic, accumulates in excess with respect to dose in fat tissue during long-term administration, and study if plasma and fat tissue concentrations are correlated with adverse effects.

Methods: Trough concentrations of amiodarone and N-desethyl-amiodarone were measured simultaneously in plasma and fat tissue, in 30 consecutive patients treated with amiodarone for 3 months to 12 years. Subcutaneous adipose tissue was obtained by needle aspiration from lumbar and abdominal areas.

Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study.

Background And Objectives: Paracetamol (acetaminophen) has occasionally been reported to interact with warfarin. The primary end-point of this study was to investigate whether paracetamol initiation potentiates the anticoagulant effect of warfarin and the mechanism of the interaction.

Design And Methods: In a double-blind placebo-controlled, randomized, cross-over study, 20 patients on stable oral anticoagulant therapy with warfarin for at least 1 month were randomized to receive placebo or paracetamol 1g four times daily for 14 days.

Which treatment for patent foramen ovale in cryptogenic stroke?

The management of a patient with a cryptogenic stroke and a patent foramen ovale (PFO) depends on the existence of identifiable causes of stroke, on the PFO characteristics, on the characteristics of the patient, on the contraindications to antithrombotic therapy, and on the preference of the patient. There is no consensus on the management of a patient with a cryptogenic stroke and a PFO, but the algorithm presented in this article seems reasonable to these authors.

Management of oral anticoagulant in clinical practice: a retrospective study of 187 patients.

Oral anticoagulant (OA) therapy is widely used in elderly patients because of the increase of indications with age (venous thromboembolism and atrial fibrillation). A particularity of France is to administer three different OAs (warfarin and more often fluindione or acenocoumarol). In an attempt to assess the particularities of managing all three OAs in elderly patients in clinical practice, we studied the modalities of anticoagulation of 187 consecutive OA therapy patients (mean age = 74.

Pharmacokinetic-pharmacodynamic modeling of the effect of triamcinolone acetonide on central macular thickness in patients with diabetic macular edema.

Purpose: To develop a population model capable of describing the profile of the effect of intravitreal triamcinolone acetonide in the treatment of diabetic diffuse macular edema.

Methods: The results of 51 injections in 37 eyes (33 patients) with diffuse diabetic macular edema were studied, by using population pharmacokinetic-pharmacodynamic modeling, without triamcinolone concentration measurements. This approach was supported by the pharmacokinetic hypothesis that the intravitreal triamcinolone concentration decreases in accordance with an exponential biphasic equation.

D-dimer can predict survival in patients with chronic atrial fibrillation.

High mean levels of D-dimers (DD), markers of fibrin product and degradation, have been reported in patients with atrial fibrillation. In order to determine the predictive value of DD, 125 consecutive patients (mean age, 78 years) with chronic atrial fibrillation without acute disease were prospectively included. DD were quantified by Liatest at inclusion.

Does paracetamol potentiate the effects of oral anticoagulants?: a literature review.

Paracetamol (acetaminophen) is the analgesic and antipyretic therapy of choice for patients receiving oral anticoagulation. It is widely used by patients in both prescription and over-the-counter products, resulting in frequent co-prescription with oral anticoagulants, especially in elderly patients. Indeed, older patients are the most likely to receive this combination of drugs because indications for both oral anticoagulation and analgesic therapy increase with age.

Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial.

Objective: To evaluate prospectively the efficacy and safety of 1 intravitreal injection of 4 mg of triamcinolone acetonide for refractory diffuse diabetic macular edema.

Design: Interventional case series.

Participants: Fifteen patients with bilateral diabetic macular edema unresponsive to laser photocoagulation.

Enhanced saquinavir exposure in human immunodeficiency virus type 1-infected patients with diarrhea and/or wasting syndrome.

The protease inhibitor saquinavir was administered to 100 human immunodeficiency virus type 1 (HIV-1)-infected patients as a single 600-mg oral dose (hard gelatin capsules) with a standard breakfast, including 200 ml of grapefruit juice, during an open-label trial to assess whether diarrhea and/or wasting syndrome has consequences on its pharmacokinetics. Three groups of patients were enrolled: group 1, asymptomatic patients (n = 30); group 2, AIDS symptomatic patients without body weight loss or diarrhea (n = 37); and group 3, AIDS symptomatic patients with severe body weight loss and/or diarrhea (n = 33). Clinical and biological data (covariates) were collected.

Defining the role of calcium channel antagonists in heart failure due to systolic dysfunction.

Calcium channel antagonists (CCAs) may either be divided into the dihydropyridines (e.g. amlodipine, felodipine, isradipine, lacidipine, nilvadipine, nifedipine, nicardipine etc.

[What are the criteria for evaluation and prevention of venous thromboembolism?].

Venous thromboembolism occurs frequently in both medical and surgical units. Although we possess the therapeutic means to prevent this condition, the question is how to assess the benefit induced by a treatment in relation to the haemorrhagic risk? The primary evaluation criteria and the evaluation method must be correctly chosen. While phlebography is the reference method for diagnosing deep venous thrombosis, the limitations associated with this method have led to the promotion of other diagnostic techniques, and clinical criteria or composite criteria are increasingly used.

Clinical trials in paediatric oncology. Recommendations for the development of new anticancer agents.

Childhood and adolescent cancers are rare diseases. Despite the progress in treatment (more than two-thirds of all cases are cured), cancer remains the leading cause of death by disease in children older than 1 year. Access to new drugs that are more efficacious or better tolerated is therefore an important public health priority.

Aspirin for the prevention of cardiovascular events in the elderly.

Aspirin (acetylsalicylic acid), the most widely used antiplatelet drug, is clinically effective for the prevention of vascular ischaemic events. Very few primary or secondary prevention trials address the benefit-risk ratio of aspirin in the elderly. In secondary prevention, it is generally accepted that the beneficial effect of aspirin in the general patient population, demonstrated by randomised controlled trials, can be extrapolated to the elderly.

Aspirin alters arterial function in patients with chronic heart failure treated with ACE inhibitors: a dose-mediated deleterious effect.

Background: By inhibiting prostaglandin synthesis, aspirin can interfere with both arterial functional and angiotensin-converting enzyme inhibitor (ACEI) properties and be deleterious in chronic heart failure (CHF).

Aim: Our aim was to prospectively evaluate the effect of aspirin on arterial functional properties in CHF patients treated with ACEIs.

Methods And Results: Over three consecutive treatment periods of 7 days, 18 patients received placebo, followed by aspirin 100 mg/day, and then aspirin 325 mg/day.

Low molecular weight heparin for the prevention of deep venous thrombosis: a suitable monitoring in elderly patients?

Monitoring of anti-Xa activity (aXa) levels is not routinely required in patients receiving enoxaparine at prophylactic dosages, since aXa is supposed to stay below the manufacturer's recommended range in patients treated for venous thrombosis (0.5-1 IU/ml). In order to aXa in elderly subjects receiving prophylactic enoxaparin, 68 consecutive patients (mean age 82.

[From the chemical product to the authorization of drug marketing].

A great number of highly qualified specialists are involved in the drug development process, mainly chemists, galenic and pharmacokinetic experts, pharmacologists and toxicologists. The 7 to 15 years development process implies preclinical studies in thousands of animals as well as clinical studies in about 3,000 patients. Various mandatory studies, regulatory requirements as well as a drug assessment process lead to the possible marketing authorization approval.