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Biomedical subjects

E Bechgaard

Publications and source records attributed to E Bechgaard.

14 recordsLinked to original sources
PubMed1991

Intranasal administration of insulin to humans.

The purpose of this review is to summarize the information and experience at present available on the intranasal administration of insulin to human subjects and to describe some of the anatomical, physiological, pharmaceutical and technological factors which can affect the absorption of insulin. An overview is given of those absorption promoters which have been used in clinical insulin studies, and the possible absorption-promoting mechanisms are discussed. This review shows that the nasal route offers a promising alternative to parenteral administration. The easier administration and the acceptance by the patients is encouraging the development of new intranasal insulin preparations.

Absorption↗
PubMed1991

Insulin-carrying microspheres, in vitro studies.

Loading and release characteristics of insulin-carrying albumin and starch microspheres have been studied in vitro. The sorption characteristics of 125I-labelled insulin onto albumin microspheres were studied and were found to be completed within 5h, and the loading capacity was found to be 0.14% w/w. Insulin did not show any sorption into the matrix of the starch microspheres. The release characteristics were analyzed by high performance liquid chromatography. About 80% was released within 5-10 min from albumin microspheres and starch microspheres, respectively.

Humans↗
PubMed1991

Study of nasal enzyme activity towards insulin. In vitro.

The possibility of insulin being enzymatically degraded in contact with the nasal mucosa has been studied in vitro. The insulin concentration was followed during 3 h incubation at 37 degrees C with freshly collected human nasal wash, isolated enzymes from pig and rabbit nasal mucosal tissue, leucine aminopeptidase and microsomal aminopeptidase, respectively. The rate of degradation with human nasal wash was found to be less than or equal to 0.02 microgram/min, which indicates that less than 0.5% of an intranasally applied insulin dose may be destroyed by local enzymes during the time of absorption. The observed degradation was not found to be limiting for an intranasal application of insulin.

Administration, Intranasal↗
PubMed1985

Contact sensitivity to chlorhexidine?

In a joint study, 2061 patients (1346 women and 715 men) were patch tested with chlorhexidine gluconate 1% in water, included in a standard test series. 48 patients (2.3%) showed a positive reaction. These were relatively more common in men (3.2%) than in women (1.9%). Positive reactions were most common in patients with leg eczema (6.8%) or leg ulcer (10.9%). Of the 48 patients who were patch test positive, 14 (2 with leg ulcer) were retested with chlorhexidine gluconate 0.01 and 1%. Only one with a leg ulcer was positive. These findings indicate that false positive reactions, known as "the excited skin syndrome", may arise from testing eczema patients in a standard series. The sensitizing potential of chlorhexidine may be very low, but the potential in patients with an eczema or ulcer of the leg has to be further evaluated.

Adult↗
PubMed1985

Acnegenicity testing in rabbits. An objective quantification method.

An objective method for the quantification of follicular hyperkeratosis is proposed for the rabbit ear assay of acnegenicity. The area (area%) of hyperkeratinized follicles, covering a stereomicroscopic photo of the epidermis, is proposed for the quantification of the response. The uniformity of two observers' quantification was evaluated in six tested formulations. The quantification of the response in area% was found to be a suitable and objective alternative to visual scoring on a graded scale. The median relative difference between two observers' area%-quantification was found to be 26%, and there was no statistically significant difference between the two observers' quantification (p greater than 0.10). An area% of 2, 7, and 15 is preliminarily suggested to be equivalent to the lower limit for scores 1, 2 and 3 respectively.

Acne Vulgaris↗
PubMed1979

Inhibition of 5-HT uptake into neurons and platelets in mice treated chronically with chlorimipramine and femoxetine.

A single treatment with 5-HT uptake inhibitors potentiates the hypermotility in mice produced by the MAO-inhibitor nialamide. The effect of nialamide on motility was studied in mice after 4 weeks of feeding with a normal diet and diets containing various concentrations of the 5-HT uptake inhibitors chlorimipramine and femoxetine. Chronic treatment with the two substances enhanced the motor effects of nialamide about equally, which indicates a preservation of the neuronal 5-HT uptake inhibition during such treatment. The effect of chlorimipramine and femoxetine was obtained at plasma levels equivalent to or lower than the steady-state plasma concentrations found in patients treated with two 5-HT uptake inhibitors. Determination of decreased blood 5-HT after the 4 weeks of treatment was used as an in vivo test for inhibition of 5-HT uptake into platelets. Femoxetine was a much weaker depletor of blood 5-HT than chlorimipramine. These results indicate that blockade of neuronal 5-HT uptake is obtained at lower doses of femoxetine than blockade of 5-HT uptake into platelets. In contrast, chlorimipramine presumably inhibits 5-HT uptake into neurons and platelets at about the same dose.

Animals↗
PubMed1979

Pharmacokinetics of femoxetine in man.

The pharmacokinetics of a structurally new 5HT-uptake inhibitor, femoxetine (FG 4963), with antidepressant properties have been investigated in man using a radioactive as well as a non-labelled substance. A two compartment open model gives a good description of the data, both after oral and intravenous administration. The substance was almost completely absorbed after an oral dose, but only 5-10% reached the systemic circulation due to extensive first pass metabolism. The metabolites had distribution and excretion rates similar to the parent compound. Only a small part (less than 2%) was excreted as femoxetine in the urine. The urinary excretion of the parent compound varied more than a 100-fold depending on the pH of the urine. The urine pH, however, did not influence the plasma concentration of femoxetine. Most of the substance (up to 80%) was eliminated by urinary excretion of metabolites, and only a small part of the radioactive dose was excreted in the faeces (up to 11%). The pharmacokinetic parameters were not found to be dose dependent in the range investigated, but it was not possible to decide whether the bioavailability was dependent on the dose. The variation between subjects was rather large, giving only a limited possibility for prediction of the plasma concentration from one subject to another.

Administration, Oral↗
PubMed1979

Paroxetine: pharmacokinetics, tolerance and depletion of blood 5-HT in man.

The tolerance of paroxetine (FG 7051), as well as its pharmacokinetics and reduction of 5-HT in blood, has been investigated in man. Three normal, healthy volunteers were administered the single doses 10, 25, 50, and 75 mg orally, and three volunteers received 10, 25, and 50 mg per day for seven or fourteen days. No toxic effect on blood, kidney, liver, heart or general condition was found by chemical and physical examinations. The pharmacokinetic studies revealed a dose dependent systemic availability, a rather slow elimination (t1-z2 = approximately 16 hrs), a good fit to one compartment open model, and an almost complete metabolism of the substance. 25 mg paroxetine per day gave a maximal reduction of 5-HT in the blood within 2--3 weeks (to approximately 0.03 microgram/ml). The 5-HT levels returned to the basic levels during a three to four weeks drug-free period.

Administration, Oral↗
PubMed1978

Potent depletion of 5HT from monkey whole blood by a new 5HT uptake inhibitor, paroxetine (FG 7051).

The potent 5-hydroxytryptamine (5HT) uptake inhibitor FG 7051 (paroxetine, INN) was administered to rhesus monkeys in doses of 1.0, 2.5 or 7.5 mg/kg by oral gavage once daily for 13 weeks. Blood samples for analysis of 5HT in whole blood and paroxetine in plasma were taken prior to and after 1, 4 and 13 weeks of treatment. The lowest dose 1 mg/kg caused 30% depletion of 5HT in whole blood with a level of paroxetine in plasma below 2 ng/ml. Doses of 2.5 mg/kg produced an 85% depletion of 5HT and a steady state plasma concentration of about 5 ng paroxetine/ml, while 7.5 mg/kg caused a 93% depletion of 5HT and a steady state plasma concentration of 100--450 ng paroxetine/ml. There was no concentration-dependent 5HT reduction with the highest dose level suggesting that maximal depletion was produced by concentrations below 100 ng/ml. The results showed that paroxetine is a strong depletor of 5HT from whole blood of monkeys conceivably because it inhibits 5HT uptake inhibition. The effect of the drug reached its maximum within 1 week and no tolerance developed during 13 weeks.

Animals↗
PubMed1977

Determination of (+)-(3R), (4S)-3-[(4methoxyphenoxy)methyl]-1-methyl-4-phenylpiperidine hydrochloride (FG 4963) in biological fluids using competition for adsorption to glass.

A procedure has been developed for the gas chromatographic determination of a structurally new 5HT-uptake inhibitor with antidepressant properties (FG 4963) in plasma and urine. The method involves an extraction from alkaline solution with n-pentane, and a quantitative determination by gas chromatography using an internal standard and a nitrogen-sensitive detector. The binding of FG 4963 to glass during storage and evaporation necessitates the addition of a structurally similar compound to the vials used for collection of the blood and urine, in order to compete for the binding sites of the glass. The method is suitable for pharmacokinetic and clinical studies, the sensitivity being ca. 5 ng/ml in plasma and 1 ng/ml in urine and the precision being 10-15% for concentrations greater than 10 ng/ml.

Adsorption↗