Enhancing the therapeutic responsiveness of photodynamic therapy with the antiangiogenic agents SU5416 and SU6668 in murine nasopharyngeal carcinoma models.

Background: Photodynamic therapy (PDT) is a promising therapeutic modality using a tumor localizing photosensitizer and light to destroy tumor cells. A major limitation of PDT is tumor recurrence, which is partly due to neovascularization.

Purpose: The objective of the present study was to determine whether combination therapy with PDT and antiangiogenic agents (i.

The role of the dermatology nurse in atopic dermatitis management.

The dermatology nurse plays a unique role in managing atopic dermatitis (AD). Education and prevention are the primary focus of the dermatology nurse, and he or she can also play a vital role as a patient advocate.

[Bioequivalence and therapeutic exchange of pharmaceutical specialties: application to cyclosporin in renal transplantation].

The aim of this study was to perform a quantitative meta-analysis of the average bioequivalence criteria between Sandimmun and Sandimmun Neoral in kidney transplant patients, and to review the new bioequivalence criteria and their application to generic formulation of cyclosporin. In Medline, we searched for clinical trials evaluating the bioequivalence between Sandimmun and Sandimmun Neoral in kidney transplant patients and we collected the information regarding the bioequivalence, study design, sample size, and time post-transplant. The effect was measured by the Wolf method; publication bias was evaluated by the Galbraith method and the Rosenthal formula was used to calculate the number of additional studies with no statistical differences needed to get a statistically non-significant overall estimation.

Systolic hypertension, arterial stiffness, and vascular damage: role of the renin-angiotensin system.

The field of hypertension is entering an exciting new era in which new concepts in basic and clinical science are being rapidly translated into new recommendations for clinical practice. It is now readily apparent that an age-related increase in stiffness of the walls of the large arteries causes the predominant hemodynamic characteristic of hypertension in later life: increased systolic blood pressure. Systolic hypertension is now recognized to have greater prognostic significance than diastolic hypertension, and it is also known that the effective treatment of systolic hypertension confers a proportional benefit in risk reduction.

Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine.

Aims: To determine whether repeated once daily administration of grapefruit juice altered the pharmacokinetics or pharmacodynamics of the calcium antagonist amlodipine.

Method: S The effects of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral and intravenous amlodipine were assessed in 20 healthy men in a placebo-controlled, open, randomized, four-way crossover study using single doses of amlodipine 10 mg. For 9 days beginning with the day of administration of amlodipine, grapefruit juice (or water control) was given once daily, and blood samples, blood pressure and heart rate measures were obtained.

Pulmonary function and airway responsiveness in mild to moderate asthmatics given repeated inhaled doses of zanamivir.

Zanamivir is a potent and specific inhibitor of influenza A and B virus neuraminidase, that is now approved for the treatment, and is currently under development for the prophylaxis of influenza. To assess the safety of this drug in asthmatics, 13 subjects with mild/moderate asthma [forced expiratory volume in 1 sec (FEV1)> or =70% predicted, reversibility of FEV1 to salbutamol > or =15%, concentration of methacholine causing a drop of 20% in the FEV1 (PC20FEV1)< or =8 mg ml(-1)], were recruited to a double-blind, randomized, placebo controlled, two way cross-over study. Subjects received 10 mg zanamivir as a dry powder (2 x 5 mg blisters via a Diskhaler Sovnn Plastics Ltd.

Pharmacoscintigraphic evaluation of lung deposition of inhaled zanamivir in healthy volunteers.

Objective: The objective of this study was to determine the sites of zanamivir deposition in the respiratory tract and the pharmacokinetics of zanamivir after oral inhalation from the Diskhaler device and from a prototype of a novel breath-activated device.

Design: This was a 2-period block-randomised study in which participants inhaled zanamivir from a Diskhaler and/or the prototype device on separate days.

Study Participants: 13 healthy volunteers (5 men and 8 women) aged 20 to 42 years (mean age 29 years) and weighing 54.

Effect of renal impairment on the pharmacokinetics of intravenous zanamivir.

Objective: Zanamivir is eliminated almost exclusively by renal excretion. This study evaluated the effect of renal impairment on the pharmacokinetics of intravenous zanamivir.

Design: This open-label study compared individuals with mild/moderate or severe renal impairment, as defined by creatinine clearance (CLCR), with healthy participants.

Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers.

Objective: The objective of these studies was to examine the clinical pharmacokinetics and safety of zanamivir, an influenza A and B virus neuraminidase inhibitor, when administered to healthy volunteers.

Design: The safety, tolerability and pharmacokinetics of zanamivir administered by a number of routes were assessed in randomised, double-blind and placebo-controlled studies. The study of absolute oral bioavailability had an open design.

Clinical pharmacology of atovaquone and proguanil hydrochloride.

Background: Atovaquone and proguanil hydrochloride is a new antimalarial combination that is used for treatment and prophylaxis of malaria.

Methods: The clinical pharmacology of atovaquone and proguanil was reviewed.

Results: Atovaquone is a highly lipophilic compound with low aqueous solubility, the absorption of which is limited by the rate and extent of dissolution.

Pharmacokinetics of grepafloxacin.

Grepafloxacin is a fluoroquinolone antibiotic which is rapidly absorbed in healthy volunteers following oral dosing. It reaches peak plasma levels around 2 h after administration, then declines bi-exponentially, with an extended half-life of around 12 h. Grepafloxacin is eliminated primarily through metabolism and is excreted mainly in the faeces.

The Renin-Angiotensin and fibrinolytic systems co-conspirators in the pathogenesis of ischemic cardiovascular disease.

In vitro and in vivo data provide evidence for an interaction between the renin-angiotensin and fibrinolytic systems. Angiotensin-converting enzyme (ACE) is strategically poised to regulate this interaction. ACE catalyzes the conversion of angiotensin I to angiotensin II (Ang), and Ang II stimulates release of PAI-1, the major inhibitor of tissue-type plasminogen activator (t-PA) and urokinase in the vasculature.

Pharmacokinetics of intravenous fluticasone propionate in healthy subjects.

1. Fluticasone propionate (FP) is a potent glucocorticoid used in the treatment of asthma. Prior to reporting the pharmacokinetics following the inhaled and oral routes, the pharmacokinetics need to be established following intravenous dosing.

Clinical pharmacology of HFA134a.

The safety, tolerability and pharmacokinetics of the chlorine-free propellant HFA134a were assessed in healthy subjects after single and repeat doses. Absorption and disposition were investigated in healthy subjects and severe chronic obstructive pulmonary disease (COPD) patients using labelled HFA134a. There were no clinically significant changes in vital signs, ECG, pulmonary function tests and laboratory parameters measured.

Quality of adverse drug experience reports submitted by pharmacists and physicians to the FDA.

The US Food and Drug Administration (FDA)'s Spontaneous Adverse Experience Reporting System is a computerized database with over one million adverse drug experience (ADE) reports. In 1992, the FDA received over 100,000 ADE reports and pharmacists were major contributors to these reports. In 1993, the FDA launched MEDWatch, a new initiative to enhance direct reporting of adverse events by health professionals.

Acute and chronic effects of nonsteroidal antiinflammatory drugs on glomerular filtration rate in elderly patients.

To assess the effects of nonsteroidal antiinflammatory drugs (NSAIDs) on glomerular filtration rate (GFR) in elderly patients with and without renal insufficiency, we conducted an open-label, randomized, prospective three-period cross-over study. Twenty-nine patients at least 65 years old were assigned to groups with preserved GFR (> 1.16 mL/s [70 mL/min]) or with renal insufficiency (GFR 0.

Salmeterol inhaler using a non-chlorinated propellant, HFA134a: systemic pharmacodynamic activity in healthy volunteers.

Background: Metered dose inhalers for the treatment of asthma use chlorofluorocarbons as propellants. These face an international ban due to their effect on the ozone layer. Salmeterol has been reformulated using the non-chlorinated propellant Glaxo inhalation grade HFA134a.

Antagonism of the effects of clonidine by the alpha 2-adrenoceptor antagonist, fluparoxan.

1. The effects of fluparoxan, an alpha 2-adrenoceptor antagonist, on the pharmacodynamic changes induced by clonidine were investigated in this placebo-controlled, double-blind, two-period, cross-over study in 16 healthy male volunteers (aged 19 to 44 years). 2.

Volunteer models for predicting antiemetic activity of 5-HT3-receptor antagonists.

1. Selective 5-HT3-receptor antagonists are highly effective in preventing nausea and vomiting associated with chemotherapy, radiotherapy and surgery. Their pharmacological activity may be determined in vitro and in animal models of emesis.

Does tachyphylaxis occur to the non-pulmonary effects of salmeterol?

1. The potential for tachyphylaxis to the non-pulmonary effects of salmeterol, a long-acting selective beta 2-adrenoceptor agonist was investigated in 12 healthy male subjects in a double-blind two period crossover study design. 2.

Ipecacuanha-induced emesis: a human model for testing antiemetic drug activity.

In a double-blind, randomized, parallel-group study, five groups of 10 healthy men received single 5-minute infusions of 8 mg, 4 mg, 1 mg, 0.25 mg, or 0.1 mg ondansetron (as hydrochloride dihydrate) 30 minutes before oral administration of 30 ml syrup of ipecacuanha.

Safety and tolerance of trospium chloride in the high dose range.

The safety and tolerance of increasing single oral doses of 20, 40, 80, 120, 180, 240 and 360 mg trospium chloride (Spasmo-lyt, CAS 10405-0204) were investigated in 29 healthy male volunteers in a double-blind placebo-controlled study. Blood pressure, heart rate, ECG, pupillary diameter, salivary secretion, and subjective reports of tolerance revealed no essential differences between placebo and trospium chloride in doses up to 120 mg. Starting with single doses of 180 mg, anticholinergic effects were observed with increasing intensity, i.

Clinical effect of indolidan in congestive heart failure.

Indolidan (IN) experimentally inhibits type IV phosphodiesterase. It was administered to twelve patients (age 64 +/- 15 years) with New York Heart Association (NYHA) class 2-3 congestive heart failure in which digoxin and diuretic therapy were continued. IN was administered i.

A comparison of tablets with oral suspension formulation of dipyridamole in thallium myocardial imaging.

Dipyridamole stress thallium imaging has been widely employed to diagnose and assess the extent of coronary heart disease in patients who cannot exercise. When oral dipyridamole administration was used, a wide range of results for sensitivity, specificity, hemodynamic response and side effect profile has been reported. The authors hypothesized that the formulation used for oral administration of dipyridamole plays a major factor in this variability, and that the pulverized form of dipyridamole will achieve faster and more consistent response than the standard tablet form.