Factors Predictive of Sentinel Lymph Node Involvement in Primary Breast Cancer.

Background/aim: Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for axillary staging in patients with early-stage breast cancer. The need for therapeutic ALND is the subject of ongoing debate especially after the publication of the ACOSOG Z0011 trial. In a retrospective trial with univariate and multivariate analyses, factors predictive of sentinel lymph node involvement should be analyzed in order to define tumor characteristics of breast cancer patients, where SLNB should not be spared to receive important indicators for adjuvant treatment decisions (e.

Pharmacokinetics and pharmacodynamics of the hydroxymetabolite of glimepiride (Amaryl) after intravenous administration.

Glimepiride is a new sulphonylurea which is eliminated by the formation of a hydroxy-metabolite (hydroxy-gli) and a carboxymetabolite (carboxy-gli). Animal studies have shown hydroxy-gli to exhibit some hypoglycaemic effects while carboxy-gli does not appear to have any pharmacological activity. Pharmacokinetic and pharmacodynamic effects of hydroxy-gli were assessed in humans.

Dose linearity assessment of glimepiride (Amaryl) tablets in healthy volunteers.

Twelve healthy fasting male volunteers received glimepiride in 1, 2, 4 or 8 mg single oral doses. On the days when glimepiride was taken, the subjects were given a standardised carbohydrate diet (18 bread exchange units) and drank 125 ml of water hourly. Blood and urine samples were taken before drug administration and afterwards for up to 36 hours (blood) and 48 hours (urine) to determine serum and urinary concentrations of glimepiride and its hydroxy- and carboxy-metabolites (M1 and M2).

Absolute bioavailability of glimepiride (Amaryl) after oral administration.

Twelve healthy fasting male volunteers received a single 1.0 mg dose of glimepiride either as an intravenous injection over one minute or as a tablet. Blood and urine samples were taken before drug administration and afterwards for up to 24 hours (blood) and 48 hours (urine) to determine serum and urinary concentrations of glimepiride and its hydroxy- and carboxy-metabolites (M1 and M2).

Dose relationship of stimulated insulin production following intravenous application of glimepiride in healthy man.

This study evaluates stimulated insulin production rate (incremental AUC x MCR (metabolic clearance rate) of C-peptide) and blood glucose (BG) response after i.v. administration of glimepiride (Hoe 490, GLI, CAS 93479-97-1) (0.

Influence of cefpirome on pharyngeal and faecal flora after single and multiple intravenous administrations of cefpirome to healthy volunteers.

The effect of single and multiple 2 g doses of i.v. cefpirome on pharyngeal and faecal flora was studied in ten male volunteers.

Safety, tolerance and pharmacokinetics of cefpirome administered intramuscularly to healthy subjects.

The pharmacokinetics of cefpirome were studied in healthy male subjects following single (0.5, 1.0 and 2.

Pharmacokinetics of metamizol metabolites in healthy subjects after a single oral dose of metamizol sodium.

The linearity of the pharmacokinetics of the metamizol metabolites 4-methyl-amino-antipyrine (4-MAA), 4-amino-antipyrine (4-AA), 4-formyl-aminoantipyrine (4-FAA), and 4-acetyl-amino-antipyrine (4-AcAA) has been studied after administration to 15 healthy male volunteers of single oral doses of 750, 1500, and 3000 mg metamizol. The trial was open, randomized, and cross-over, with a one-week interval between dosing days. Metabolite concentrations in serum and urine were measured using reverse-phase HPLC.

Effects of HOE 760 (histamine H2-receptor antagonist) on diazepam pharmacokinetics.

A double-blind cross-over study of the effects of HOE 760 (histamine H2-receptor blocker) on diazepam pharmacokinetics was conducted in 12 healthy men. HOE 760 or placebo was given daily for 12 days and, after a wash-out period of 9 days, the alternate medication was given for 12 days. Diazepam 10 mg was given intravenously on day 6 of each of the 12-day periods.

Safety, tolerance and pharmacokinetics of 2.0 g cefpirome (HR 810) after single and multiple dosing.

After intravenous injection of a single dose of 2.0 g cefpirome (HR 810) and multiple doses of 2.0 g b.

Dose linearity testing of intravenous ofloxacin, a novel gyrase inhibitor.

After intravenous bolus injection of single doses of 25, 50, 75 and 100 mg of ofloxacin (HOE 280) to 34 healthy male volunteers, concentrations of unchanged drug were estimated at various times in serum and urine over 32 and 48 h. Ofloxacin concentrations were determined using high-pressure liquid chromatography (HPLC). A linear relationship between dose and Cmax (r = 0.

The effects of forskolin eye drops on intra-ocular pressure.

Two studies were performed to investigate the effects of forskolin (Hoechst Research) on intra-ocular pressure (IOP). In the first study two 1.0% formulations of forskolin eye drops were compared with placebo in 10 healthy volunteers.

Pharmacokinetics of ramipril in the elderly.

Ramipril (HOE 498) is a pro-drug of which the main metabolite (HOE 498 diacid or ramiprilat) is a potent angiotensin converting enzyme inhibitor. Thirteen healthy white volunteers (5 females and 8 males, ages 65 to 76 years) participated in a study to investigate the pharmacokinetics of HOE 498 in the elderly. After administration of 10 mg of HOE 498, sequential urine and serum specimens were obtained for assay of HOE 498 and metabolites (HOE 498-glucuronide, diacid, diacid-glucuronide, diketopiperazine and diketopiperazine acid).

The effects of metamizol on prostaglandin synthesis in man.

Clinical pharmacological investigations on the inhibition of prostaglandin synthesis are presented, comparing metamizol and indomethacin with respect to platelet aggregation, platelet thromboxane synthesis, total body PGE2-synthesis and side effects. Prostaglandin synthesis is clearly and persistently inhibited by metamizol in man.

[Effect of forskolin eyedrops on intraocular pressure in healthy males].

Suspensions of Forskolin in concentrations of 0.3; 0.6; and 1.

A radioimmunoassay for determination of glibenclamide and other sulfonylureas.

An antiserum was prepared for the determination of glibenclamide and for the estimation of other commercially available sulfonylureas. Rabbits were immunized with a glibenclamide-BSA conjugate. Tritiated glibenclamide was used as the tracer.

Pharmacokinetics and biotransformation of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S, 5S)-2-azabicyclo [3.3.0]octane-3-carboxylic acid (Hoe 498) in rat, dog and man.

After oral administration, 2 mg/kg in rat and dog, 10 mg in man, of the carbon-14-labeled angiotensin I converting enzyme inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S, 5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498), absorption (rat 56%, dog 43%, man 56%) occurred rapidly and induced maximum blood levels between 0.

Bioavailability and pharmacodynamics of a sustained-release glibenclamide product (Deroctyl) in comparison to a standard tablet formulation (Euglucon, Daonil).

Pharmacodynamics and tolerance, as well as the bioavailability of two oral dosage forms of 5 mg glibenclamide were determined in eight healthy male volunteers in a double-blind crossover study. These preparations were Euglucon (regular tablets) and Deroctyl (sustained-release capsules). Blood glucose levels were determined by the hexokinase method and serum glibenclamide, insulin, and C-peptide levels by radioimmunoassay.

Kinetics of UV-erythema in normal subjects.

In the expanding field of clinical dermatopharmacology we standardized an erythema model for testing drugs with effects on UV-induced inflammation in normal male Caucasian subjects. Using a light source with fibre-optic transmission and precise radiation characteristics, some of the shortcomings of conventional UV-application could be overcome. The radiation geometry during the various experiments was kept constant by a tube, permitting a defined area of exposure.

[Adequate and inadequate trials in "clinical" pharmacology].

Our definition, based on 14 years of practical experience, is as follows: In clinical pharmacology, a procedure is adequate if it can be used in normal subjects in a non-invasive way and if it generates relevant information concerning pharmacotherapy in patients. Six examples are discussed in detail; the variable body weight may cause wide variations, for example, in absorption characteristics; unhomogeneous groups of subjects are likely to lead to poorly reproducible results. Body position and food intake (individual eating habits) may disguise drug effects by creating additional "noise".

Standardized mental stress in healthy volunteers induced by delayed auditory feedback (DAF).

Using delayed auditory feedback (delay 0.175 s) a standardized form of mental stress was investigated in 8 healthy male volunteers. After a resting period and a period of undelayed reading, the volunteers were exposed for 5 min to the DAF stress.

Pharmacodynamic comparison of the acute effects of nomifensine, amphetamine and placebo in healthy volunteers.

In a double blind cross over trial the effects of single doses of 100 mg nomifensine, 15 mg racemic amphetamine and placebo were compared in 9 healthy volunteers. Assessments of choice reaction behavior, simple reaction time, critical flicker fusion and attention on continuous calculations were performed together with a series of self rating scales, a side-effect list and vital signs before and 90 min., 180 min.