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Biomedical subjects

H Mengel

Publications and source records attributed to H Mengel.

At least 19 recordsLinked to original sources
PubMed2005

Control of clinical coccidiosis of calves due to Eimeria bovis and Eimeria zuernii with toltrazuril under field conditions.

The efficacy of metaphylactic treatment with toltrazuril (Baycox 5% suspension) against natural infections with Eimeria bovis and/or Eimeria zuernii in calves was investigated. The study was conducted with 208 calves on five calf-rearing farms in Germany and the Czech Republic. All participating farms had a notable incidence of coccidiosis. Animals were treated 14 days after stabling in the respective facility. One group was treated with 15 mg toltrazuril/kg body weight, and a second group served as the sham-treated control. Assessment of efficacy was based on faecal consistency and oocyst excretion of E. bovis and E. zuernii, both investigated throughout the study. Duration and rate of oocyst excretion as well as number of scour days with E. bovis or E. zuernii oocyst shedding and the severity of diarrhoea were significantly lower in the toltrazuril-treated groups. It is concluded that a single metaphylactic treatment with toltrazuril controls coccidiosis of housed calves under various field conditions.

Animals↗
PubMed2005

The pharmacokinetics of escitalopram after oral and intravenous administration of single and multiple doses to healthy subjects.

The pharmacokinetics of escitalopram (S-citalopram) and its principal metabolite, S-demethylcitalopram (S-DCT), were investigated after intravenous and oral administration to healthy subjects. After intravenous infusion of escitalopram, the mean systemic clearance and volume of distribution were 31 L/h and 1,100 L, respectively. After oral administration of single or multiple doses, the absorption was relatively fast, with the maximum observed plasma or serum concentration (C(max)) attained after 3 to 4 hours. The mean half-lives were 27 and 33 hours, respectively; steady state was attained within 10 days. The area under the plasma or serum concentration time curve from time zero to 24 hours and C(max) was both linear and proportional to the dose. The apparent volume of distribution was around 20 L/kg. Comparison of the systemic and oral clearance implied a high absolute bioavailability. There was no evidence of interconversion from S-citalopram to R-citalopram either in plasma or in urine. Concurrent intake of food had no effect on the pharmacokinetics of escitalopram or its metabolite. All treatments were well tolerated.

Administration, Oral↗
PubMed2000

Lu 25-109, a muscarinic agonist, fails to improve cognition in Alzheimer's disease. Lu25-109 Study Group.

OBJECTIVE: To evaluate the therapeutic effect of the selective muscarinic receptor m1 partial agonist, m2 antagonist, Lu25-109-a compound that directly stimulates muscarinic cholinergic receptors-in patients with probable AD. METHODS: A 6-month, randomized, double-blind, placebo-controlled, parallel group trial comparing three doses of Lu25-109 with placebo was carried out. A total of 496 patients with probable AD with a Mini-Mental State Examination score between 10 and 26 were enrolled at 29 centers and randomized to placebo or Lu25-109 25, 50, or 100 mg tid. The primary efficacy measures were the AD Assessment Scale-Cognitive subscale and the AD Cooperative Study Clinical Global Impression of Change. Secondary efficacy variables included the AD Cooperative Study Inventory of Activities of Daily Living and the Behavioral Symptoms in AD Scale. RESULTS: In both an intent-to-treat and a completer's analysis there were no significant differences for either the two primary or the secondary variables. There was a trend for patients on the highest drug dose to worsen in the completer's analysis. Adverse events included dizziness, nausea, diarrhea, fatigue, increased sweating, and anorexia, all of which increased with increasing drug dose. CONCLUSION: Lu25-109, a selective partial ml agonist and an m2/m3 antagonist, failed to improve cognition in patients with mild to moderate AD.

Aged↗
PubMed1998

A bridging study of LU 25-109 in patients with probable Alzheimer's disease.

Lu 25-109 is a functionally selective partial M1 agonist with M2/M3 antagonist properties. This double-blind, placebo-controlled, two-part, inpatient bridging study was designed to evaluate the safety and tolerability of multiple oral doses of Lu 25-109 in patients with Alzheimer's Disease(AD), and to determine the maximum tolerated dose (MTD) in this population. In the first part of the study, the fixed-dose MTD was to be determined in five consecutive panels of 6 patients each (4 Lu 25-109/2 placebo). Doses for the five panels were 100, 125, 150, 200, and 225 mg tid for 7 days. Cholinergic adverse events such as increased salivation, dizziness, and gastrointestinal symptoms were observed at all doses studied. The dosing of fixed-dose panels was discontinued after 3 days at 200 mg tid due to unacceptable gastrointestinal adverse events. Thus, 150 mg tid was defined as the fixed-dose MTD. The second part of the study, conducted in a single panel of 8 patients (6 Lu 25-109/2 placebo), was designed to determine if patients could tolerate higher doses of Lu 25-109 when administered on a titration regimen. Patients were to receive doses that were 50%, 75%, 100%, 125%, and 150% of the fixed dose MTD, with dose increases every five days. The first dose, 75 mg tid, was very well-tolerated; however, as in the first phase of the study, patients did not tolerate the 200 mg tid dose. Thus, the titration regimen employed did not improve the overall tolerability of Lu 25-109.

Aged↗
PubMed1995

Adjunctive treatment of partial seizures with tiagabine: a placebo-controlled trial.

Tiagabine is a new antiepileptic drug which acts by a novel mechanism, inhibiting the reuptake of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into neurons and glia. A double-blind, placebo-controlled, crossover trial was undertaken, based upon a response-dependent design. Ninety-four patients with complex partial seizures with or without secondary generalised tonic-clonic seizures were recruited into an open screening phase and tiagabine was added to their existing drug therapy in doses titrated to reduce seizure frequency by > or = 25% or to the limit of tolerance. Forty-six responders were subsequently randomised to a double-blind crossover trial in which tiagabine was compared with placebo. Forty-two patients completed the trial. A significant reduction in the frequency of complex partial and secondary generalised tonic clonic seizures was seen. Twenty-six percent had a reduction of > or = 50% in the frequency of their complex partial seizures, and of the 27 patients who also had secondary generalised tonic clonic seizures, 63% experienced a reduction of > or = 50%. No interactions with baseline antiepileptic drugs were detected and no serious adverse reactions occurred. The commonest adverse events were tiredness, dizziness and headache. We conclude that tiagabine has promising antiepileptic effects. Further trials are underway.

Adolescent↗
PubMed1994

Tiagabine.

Tiagabine (TGB), a specific gamma-aminobutyric acid (GABA)-uptake inhibitor, is a potential new antiepileptic drug with a novel mechanism of action. In animal models of epilepsy as well as in a placebo-controlled trial in patients with complex partial seizures, TGB showed significant anticonvulsant effects. TGB was well tolerated by most patients.

Acoustic Stimulation↗
PubMed1991

Pharmacokinetics of paroxetine in patients with cirrhosis.

In a 14-day multiple-dose study the pharmacokinetics of paroxetine was investigated in 12 patients with alcoholic cirrhosis and in 6 subjects without liver disease. The dose of 20-30 mg paroxetine daily was adjusted to the reduction in liver function, as assessed by the galactose elimination capacity. Accordingly, all but two of the cirrhotic patients received 20 mg, while all six control subjects received 30 mg. Dose-corrected, trough drug concentration at steady state (CSSmin) and dose-corrected AUC24h were significantly higher in the patients with liver diseases than in the control subjects [3.4 vs 1.5 ng.ml-1 per mg paroxetine and 89 vs 43 h (ng).ml-1 per mg paroxetine]. The elimination t1/2 was prolonged [83 vs 36 h], but the difference was not statistically significant, and the cirrhotic patients were still able to clear almost all the paroxetine by metabolism. All but two patients with cirrhosis experienced nausea during the first two or three days after the first dose, while none of the controls had this symptom. The study showed slower elimination of paroxetine and consequently higher plasma levels in patients with cirrhosis, suggesting that in the latter the dose of paroxetine should be in the lower end of the therapeutic range.

Adult↗
PubMed1990

Pharmacokinetics of the anxiolytic beta-carboline derivative abecarnil in the mouse, rat, rabbit, dog, cynomolgus monkey and baboon. Studies on species differences.

The pharmacokinetics of abecarnil (isopropyl 6-(benzyloxy)-4-(methoxymethyl)-9H-pyrido [3,4-b] indole-3-carboxylate, ZK 112 119) were studied in the mouse, rat, rabbit, dog, cynomolgus monkey and baboon using 14C-labeled drug and HPLC with fluorescence detection for measurement of unchanged drug. Abecarnil was rapidly and completely absorbed after oral doses of 10 mg/kg. At higher doses, absorption was prolonged and incomplete in the cynomolgus monkey. The bioavailability of abecarnil was 20-30% in all the species investigated. The terminal half-life of the unchanged drug in plasma was relatively similar in all species (0.6-1.7 h). Abecarnil was able to pass the blood-brain barrier achieving concentrations in the brain similar to those in plasma. Tissue distribution of labeled compounds was rapid with highest concentrations in the liver, adrenals, kidneys and pancreas followed by the bone marrow, lungs, heart, fat, spleen, ovaries and thyroid gland. Excretion of radiolabeled compounds proceeded predominantly in the feces of the rat, the rabbit and the cynomolgus monkey.

Animals↗
PubMed1989

Determination of an oxadiazole-substituted 1,4-benzodiazepine in plasma by high-performance liquid chromatography with ultraviolet detection and by a radioreceptor assay.

A high-performance liquid chromatographic (HPLC) method for the determination of an oxadiazole-substituted 1,4-benzodiazepine [3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5,6-dihydro-5-methyl-6-oxo -4H-imidazo[1,5a] [1,4]benzodiazepine] in plasma has been developed and compared with a radioreceptor assay. The results given by the two methods were in good agreement, with detection limits of ca. 1 ng/ml (signal-to-noise ratio = 3). The radioreceptor method is preferred for the monitoring of toxicological and other well controlled studies, while HPLC is preferred where greater specificity is essential. Further, the HPLC assay is applicable over a much wider concentration range.

Animals↗
PubMed1989

Determination of beta-carboline derivatives in biological samples by high-performance liquid chromatography with fluorescence detection.

An assay procedure for measuring plasma, urine, and feces levels of seven beta-carbolines and possible metabolites is described. The drugs are extracted with diethylether or, alternatively, with a commercially available automated extraction device after adding an appropriate internal standard. Separation from matrix constituents is performed by reversed-phase high-performance liquid chromatography (HPLC) followed by fluorescence detection. The carboxylic acid metabolites of the beta-carbolines have to be esterified before HPLC measurement. The detection limits are 0.2 ng/mL for beta-carbolines and 2 ng/mL for their metabolites. Plasma levels and pharmacokinetic parameters of six different beta-carbolines in healthy male volunteers following iv or po treatment are described. Total clearance ranged from 17 to 52 mL/min/kg and the terminal half-life ranged from 1 to 4 h. The absolute bioavailability exhibited a range from less than 1 to 61%.

Administration, Oral↗
PubMed1989

The influence of the duodenal passage on postprandial neurotensin release in dogs.

All types of gastric resections induce an abnormal release of gastrointestinal hormones. The missing duodenal passage seems to be the most important factor for these disturbances. In the present study we have examined the effect of exclusion and restoration of the duodenal passage on the postprandial release of neurotensin in dogs. After feeding a standard canned dog meal, exclusion of the duodenal passage by a Billroth-II-resection caused a significant increase in postprandial neurotensin release compared to the control group (peak levels 52 +/- 5.6 to 29 +/- 6 pg/ml preoperatively, integrated output 2132 +/- 228 to 3604 +/- 213 pg/ml x 150 min. p less than 0.05). Reconstruction of the duodenal passage by the Biebl-Henly-Soupault-procedure tended the elevated neurotensin levels towards normal (peak levels 36 +/- 4.8 pg/ml, integrated output 2448 +/- 236 pg/ml x 150 min., p less than 0.05). From our data we conclude that changes in intestinal transit time are responsible for the pathological increase in neurotensin release after exclusion of the duodenal passage.

Animals↗
PubMed1989

Paroxetine: pharmacokinetic and antidepressant effect in the elderly.

To evaluate the pharmacokinetic properties, efficacy, and tolerability of paroxetine in elderly depressed patients, a clinical study was set up--initially at Aalborg Psychiatric Hospital in Denmark, and subsequently at the University Hospital in Linköping, Sweden. A total of 21 patients with a median age of 72 years were included in the study. After a single dose of 20 or 30 mg of paroxetine followed by two drug-free days, treatment continued with 20 or 30 mg daily for seven weeks. The majority of patients showed a continuous reduction in their HAMD scores, starting in the second week of treatment. Paroxetine was well tolerated at the doses given, and side-effects were mostly mild and transient. Steady-state, pre-dose plasma levels of paroxetine showed considerable variability, and the median steady-state concentration was higher in elderly patients compared with data from a previous study in young volunteers. Elimination half-lives also showed variability between these elderly patients, but tended to be longer after cessation of multiple dosing than after a single dose. They also tended to be longer than in the young volunteers. The results of this study do not advocate reduced doses of paroxetine in the elderly, but further studies are warranted.

Aged↗
PubMed1986

Femoxetine and cimetidine: interaction in healthy volunteers.

The possibility of a pharmacokinetic interaction between femoxetine and cimetidine has been evaluated in 8 healthy volunteers. Two volunteers received single doses of femoxetine, and 6 were given multiple doses of femoxetine for 7 days with and without concurrent cimetidine. No influence of cimetidine was observed on the kinetics of single doses of femoxetine, but after multiple doses the plasma concentration of femoxetine was significantly increased. Similarly, the AUC at steady state tended to be increased, but not to a significant extent. Concurrent cimetidine did not cause a reduction in the AUC of the active desmethyl metabolite. It is recommended that femoxetine is given in reduced doses (e.g. 400 mg) when administered with cimetidine.

Adult↗
PubMed1984

Femoxetine clearance in patients with liver cirrhosis.

The pharmacokinetics of femoxetine (a 5-HT uptake inhibitor with antidepressive effect) was studied in 12 patients with liver cirrhosis and in 6 healthy controls after a single oral dose of femoxetine HC1. The average blood concentration of femoxetine, as assessed by the values of AUC (area under the plasma concentration/time curve), was significantly higher in the patients with liver cirrhosis than in the healthy controls in spite of dose reduction in the patients. The elimination half-life of femoxetine was within the normal limits in most of the patients. The oral clearance of femoxetine was considerably lower in patients, (0.65-4.02 1/hr/kg) than in the controls (8.13- greater than 50 1/hr/kg). It was not directly related to the metabolic function of the liver, measured as the galactose elimination capacity being 0.015-0.024 mmol/min./kg and 0.033-0.041 mmol/min./kg, respectively. When treating patients with reduced liver function, it is recommended to reduce the doses and to monitor closely the plasma levels.

Adult↗
PubMed1983

Hepatic elimination of femoxetine in pig during intravenous infusion.

Hepatic elimination of femoxetine was studied in six anaesthetized pigs during intravenous administration. Femoxetine was given into a jugular vein as a constant infusion of 0.4-7.2 mg/min. in five pigs and as a bolus injection of 383 mg in one pig. The hepatic extraction was high (92-98%) corresponding to earlier findings of 91-99% when femoxetine was infused into the portal vein in pig or given orally to man. The urinary excretion was low, less than 5% of the dose, and the estimated extrahepatic metabolism was not significantly different from zero.

Animals↗
PubMed1983

[Bacterial antibodies and isoagglutinins in intravenous immunoglobulin preparations].

Various lots of intravenous immunoglobulins for passive immunization should contain almost the same, broad, antibody profile and provoke very low frequencies of untoward reactions. From 1976-1982 a study was undertaken to measure the level of antibodies directed against tetanustoxin, diphtheriatoxin, streptolysin O, staphylolysin, and salmonella in up to 82 lots. It is interesting to note that the measured level of antibodies in intravenous immunoglobulins varied only slightly as well qualitatively as quantitatively with one exception: an immunoglobulin of placental origin. The amount of tetanusantitoxin in the majority of lots of that preparation was ten-fold lower than that of the other immunoglobulins. Intravenous immunoglobulins contain generally 3-6 IE/ml antistaphylolysin, 600-1200 IE/ml antistreptolysin O, 10-20 IE/ml tetanusantitoxin, and 1-2 IE/ml diphtheriaantitoxin. Antibodies to salmonella could not be demonstrated. Some of the lots exhibited isoagglutinins up to a dilution of 1 : 4.

Agglutinins↗