Pain related to Optiva 2, Biovalve, and Venflon 2 intravenous catheters.

Pain related to the insertion of intravenous catheters is a major issue for many patients. This study investigated differences in pain on insertion for three different catheters - Optiva 1, Biovalve and Venflon 2 - as assessed by 100 volunteers. Clinicians also assessed a variety of parameters related to their overall ease of use. This study demonstrates that Optiva 2 can offer significant benefits for both patient and clinician. Pain on insertion was significantly lower with Optiva 2 than with Venflon 2, but comparable with Biovalve. Ease of insertion and flashback were significantly better for Optiva 2 than for Venflon 2, but similar to Biovalve. For the parameters 'ease of catheter advancement' and 'overall ease of use', the operators rated Optiva 2 significantly better than Biovalve and Venflon 2.

Pharmacodynamics of single doses of the novel immunosuppressant FTY720 in stable renal transplant patients.

FTY720, a new and potent immunosuppressant, causes in animal models a rapid, reversible reduction of all subsets of peripheral blood lymphocytes, inducing their migration to secondary lymphoid organs. In this human phase I trial, the pharmacodynamics of single oral doses of FTY720 were evaluated. A randomized, double-blind, placebo-controlled, time-lagged study of six different single ascending oral doses of FTY720 ranging from 0.25 to 3.5 mg was conducted in stable renal transplant patients receiving a cyclosporine-based regimen. Absolute and subset lymphocyte counts, as well as absolute differential leukocyte counts, were determined by differential blood counts and flow cytometry at screening and multiple intervals thereafter. A pharmacodynamic model was established. Twenty-four single doses of FTY720 that were administered caused a transient, reversible pan-lymphopenia within 4 h. Lymphocyte subgroup analysis revealed that almost all subsets declined, with CD4- and CD45RA-positive cells being affected the most. Natural killer cells, granulocytes and monocytes were not influenced by FTY720. The lymphocyte count returned to baseline within 72 h in all dosing cohorts except the highest. Pharmacokinetik/pharmacodynamic modelling revealed a nonlinear dose effect and resulted in a good fit with observed values. These data show that FTY720 is highly effective in humans, with single oral doses of FTY720 ranging from 0.25 to 3.5 mg causing a reversible selective panlymphopenia.

Pharmacokinetic interaction study of a fixed combination of 500 mg acetylsalicylic acid/30 mg pseudoephedrine versus each of the single active ingredients in healthy male volunteers.

UNLABELLED: Acetylsalicylic acid (CAS 50-78-2, ASA) and pseudoephedrine (CAS 90-82-4, PSE) both are remedies given together for the treatment of the symptoms of a common cold, i.e. mainly nasal congestion, running nose, sore throat and headache. The aim of this open, randomized, three-factorial (three-treatment, three-period, six-sequence) Latin Square clinical study was to investigate if there were any pharmacokinetic interactions between ASA and PSE when given as fixed combination of 500 mg ASA/30 mg PSE.HCl. Lack of interaction was assessed by determination of pharmacokinetic characteristics and relative bioavailability of both substances and salicylic acid (CAS 69-72-7, SA), administered in combination and as equally single dosed drugs. In total, the data of 12 healthy male volunteers were included into the pharmacokinetic evaluation. Primary target parameters were ratios combination/equally dosed single drugs of AUCnorm and Cmax, norm of ASA, its metabolite SA and PSE. The primary target parameters were analyzed using an analysis of variance (ANOVA) after logarithmic transformation of the data. 90% confidence intervals were calculated for the geometric means of ratios using the mean square error term of the ANOVA. RESULTS: Bioequivalence was given for AUCnorm and Cmax, norm for all ratios calculated. No interaction was found for AUCnorm and Cmax, norm between the fixed combination ASA/PSE and the equally single dosed drugs as reference. The supplementary evaluation for the non-normalized original parameters AUC and Cmax also revealed bioequivalence. All treatments were safe and well tolerated.

Efficacy and safety of a Butcher's broom preparation (Ruscus aculeatus L. extract) compared to placebo in patients suffering from chronic venous insufficiency.

Extracts from Butcher's broom rhizome (Ruscus aculeatus) have been widely used in the oral treatment of lower leg edema in patients with chronic venous insufficiency. The aim of the present multi-center, double-blind, randomized, placebo-controlled trial was to confirm the efficacy and safety of a ruscus extract (Fagorutin Ruscus Kapseln) according to the latest scientific standards. 166 women suffering from chronic venous insufficiency (Widmer grade I and II, CEAP (Clinical signs, Etiological classification, Anatomic distribution, Pathophysiology) 3-4) were included. The data of 148 patients (30-89 years, 150-182 cm height, 49-97 kg body weight) with a mean disease duration of 14.6 years in the ruscus extract group and 15.1 years in the placebo group were eligible for the intent-to-treat-analysis. The primary parameter was the area under baseline of the leg volume changes over 12 weeks (AUB0-12). Secondary parameters were the changes in circumference of the lower leg and the ankle, changes in subjective symptoms and quality of life, the overall efficacy and tolerability and safety parameters. The study was carried out according to the guidelines for testing drugs for chronic venous insufficiency. There were significant differences between the treatment groups ruscus and placebo for the AUB0-12 (-827 ml x day), for the change of leg volume after 8 and 12 weeks of treatment (-16.5 ml and -20.5 ml), for changes in ankle and leg circumferences after 8 and 12 weeks of treatment, and for the changes in subjective symptoms, heavy tired legs and sensation of tension (week 12). For the changes in the symptoms heavy lower legs, sensation of tension, and tingling sensation a significant positive correlation with the changes in leg volume was shown. Overall assessment of efficacy was significantly better for ruscus extract compared to placebo. Overall tolerability for both treatments was assessed as good and very good. Of all 48 adverse events occurring in both treatment groups, 22 were reported in the ruscus group, one of them was considered to be related to the study medication (unlikely). Considering the study duration of three months it is concluded, that ruscus extract, in the recommended daily dosage according to the German monograph, is a safe and effective treatment for patients suffering from chronic venous insufficiency.

First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients.

FTY720 is a novel immunomodulator to be developed for use in organ transplantation. The primary objective of this study was to measure safety, single-dose pharmacokinetics, and pharmacodynamics in stable renal transplant patients-the first human use of FTY720. This study used a randomized, double-blind, placebo-controlled design that explored single oral doses of FTY720 from 0.25 to 3.5 mg in 20 stable renal transplant patients on a cyclosporine-based regimen. Safety assessments and blood samples were taken predose and at multiple time points during a 96-h period postdose. Standard pharmacokinetic parameters were derived from the FTY720 whole blood concentrations, measured by HPLC/MS/MS. FTY720 was well tolerated, with no serious adverse events. Transient, asymptomatic bradycardia occurred after administration in 10 of 24 doses of FTY720. Pharmacokinetics are characterized by a prolonged absorption phase; the terminal elimination phase started 36 h after the administration, with elimination half-life (t(1/2)) ranging from 89 to 157 h independent of dose. Maximum plasma concentration and AUC were proportional to dose with low intersubject variability, the apparent volume of distribution (V(d)/F) ranged from 1116 to 1737 L. FTY pharmacodynamics were characterized by a reversible transient lymphopenia within 6 h, the nadir being 42% of baseline. The lymphocyte count returned to baseline within 72 h in all dosing cohorts except the highest. Single oral doses of FTY720 ranging from 0.25 to 3.5 mg were well tolerated and caused a reversible selective lymphopenia. Transient, but asymptomatic bradycardia was the most common adverse event. The long t(1/2) suggests less frequent dosing intervals. The size of V(d)/F is in excess of blood volume, consistent with widespread tissue distribution