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Biomedical subjects

W Ritter

Publications and source records attributed to W Ritter.

At least 127 records · Page 7Linked to original sources
PubMed1985

The metabolism of muzolimine.

The metabolism of muzolimine, 3-amino-1-(3,4-dichloro-alpha-methyl-benzyl)-2-pyrazoline-5-one has been studied both in vivo and in vitro in various animal species. Using unlabelled muzolimine the major urinary metabolite in all species studied has been shown by chromatography and mass-spectrometry to have properties identical to synthetic N'-(1-aminoethylidene)-3,4-dichloro-acetophenone hydrazone. In addition, 3,4-dichloroacetophenone, 3,4-dichloromandelic and 3,4-dichlorobenzoic acids have been detected and quantified using GLC techniques. In vitro experiments using hepatic microsomal preparations from various species show that cleavage across the C-N1 bond occurs yielding 3,4-dichloroacetophenone and 3-amino-2-pyrazoline-5-one. The hydrazone was the major metabolite produced by these systems. Moreover, this compound also appears as the major metabolite in faecal extracts. Reverse-Phase High-Performance Liquid Chromatographic techniques have been employed for analysis of in vitro metabolism of muzolimine and confirmed the formation of the above metabolites.

Animals↗
PubMed1985

Pharmacokinetics of muzolimine after acute and chronic dosing in hypertensive patients with mild renal insufficiency.

Pharmacokinetics and clinical effects of muzolimine were investigated in 6 hypertensive patients with incipient renal insufficiency. Muzolimine plasma levels were determined after the first dose and after 8 weeks of treatment with muzolimine (20 mg o.d.). The area under the curve of muzolimine plasma levels was greater after 8 weeks than after the first dose. Also, peak plasma concentrations were higher after 8 weeks; however, muzolimine half-lives in the beta-phase were unchanged. Blood pressure and body weight decreased with time. Muzolimine was well tolerated.

Adult↗
PubMed1985

Diuretic effect and pharmacokinetic data observed at different stages of chronic renal failure with 240 mg of muzolimine.

Muzolimine (240 mg) was administered orally to 24 patients with chronic renal failure. In five patients with creatinine clearance ranging between 10 and 30 ml/min and five others with creatinine clearance lower than 10 ml/min, urinary output was measured in periods of 24 hours before, and 0 to 4, 4 to 10, 10 to 24, 24 to 48, 48 to 72 hours after administration of the drug. The amounts of sodium, chloride, potassium and urea excreted in each sample were determined. Our results show that the diuretic activity of muzolimine 240 mg in these patients is excellent, especially in the first four hours after its administration. Pharmacokinetic data observed in advanced renal failure (creatinine clearance between 10 and 30 ml/min) are similar to those observed in healthy subjects or patients with normal renal function. However, attention should be paid to possible accumulation of the drug in terminal renal failure (creatinine clearance lower than 10 ml/min) because a significant increase of the terminal half-life of the drug is observed in these patients. Dialysibility of the drug in haemodialysis and during chronic ambulatory peritoneal dialysis is poor.

Adult↗
PubMed1985

Clinical study of muzolimine in acute renal failure, pharmacodynamics and pharmacokinetics.

UNLABELLED: The aim of this study was to test the efficiency of muzolimine in patients with acute renal failure (ARF). METHODS: 6 patients, all males, 46 to 78 years old (mean 67.3 +/- 12.5) suffering from acute renal failure as a complication of a surgical procedure (4 cases) or a medical disease (2 cases) were selected. Creatinine clearance rates were below 20 ml/min for all subjects except one (mean: 14.4 ml/min range 4-34), blood urea levels from 21 to 65 mmol/l (mean = 36.4); mean urinary output, during the 24 hours preceding the study (D-1) was 100.4 +/- 57 ml/h (range 36-208) without any diuretic treatment. No patient was on dialysis. On the treatment day a single oral dose of muzolimine (240 mg) was administered in the morning. During the treatment day (D0) and the post treatment day (D + 1), pharmacodynamics and pharmacokinetics were evaluated. Mean urinary output increased from 1.67 +/- 0.95 ml/min, at D-1 to 3.24 +/- 2 ml/min at D0 (NS), with great differences between patients. The main effect was noted between 0 and 6 hours after the ingestion of muzolimine. The mean electrolyte output increased from D0 to D1 for Na+ (0.1 mmol/min +/- 0.08----0.25 +/- 0.1-NS), K+ (0.05 mmol/min +/- 0.02----0.08 +/- 0.07-NS), Cl- (0.07 +/- 0.07 mmol/min----0.30 +/- 0.12 p less than 0.05) and Ca++ (1.89 +/- 1.89 meq/24 h----4.1 +/- 2 NS), with large individual variations. Mean urea output increased slightly in only 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1984

Influence of muzolimine on arterial wall elastin.

Muzolimine, 3-amino-1-(3,4-dichloro-alpha-methylbenzyl)-2- pyrazolin -5-one, an antihypertensive and diuretic drug, accumulates in the arterial tissue of rats and dogs after oral administration. Two weeks after the administration of 3 mg [14C]muzolimine, the aorta of rats contained 60-300 times more 14C-radioactivity/weight unit than the skin or tail tendon. The 14C-radioactivity was exclusively bound to the isolated aortic elastin and corresponded to 0.04% of the applied muzolimine dose. Up to ca 250 ng bound muzolimine/mg elastin was found in the aorta of dogs treated with non-labelled muzolimine for 52 weeks. The elastin-bound [14C]muzolimine was not extractable by organic solvents or by weak acids or bases but was released in a soluble form by pancreatic elastase and extracted from the elastase digest by dichloromethane. In the dichloromethane extract muzolimine was detected by HPLC and HPTLC, and was identified by mass spectrometry. Muzolimine pretreatment of rats for 2 months did not influence the elastin content of arterial tissue or [3H]glycine incorporation into aortic elastin under organ culture conditions, but after labelling the elastin with [4,5-3H]lysine, the [3H]desmosine and [3H]-isodesmosine isolated from the elastin of muzolimine-pretreated rats and incorporated under organ culture conditions was lower than that of control animals. In addition, aortic elastin of rats pretreated for 2 months with 800 ppm muzolimine in the diet was more resistant to elastase degradation. This effect might give some implications for muzolimine in the therapy of cardiovascular disorders with impaired arterial elastin metabolism.

Animals↗
PubMed1984

Determination of nafazatrom in body fluids by high-performance thin-layer chromatography with post-chromatographic derivatization.

A sensitive, accurate and specific high-performance thin-layer chromatographic method has been developed for determination of nafazatrom, a pyrazolinone derivative with antithrombotic and antimetastatic activity. Because of the instability of the drug during clean-up procedures, nafazatrom is recovered from plasma and urine with a single extraction and the extract is spotted directly onto the chromatographic plate. The specificity of the assay was increased by post-chromatographic derivatization with 4-dimethylaminobenzaldehyde. Up to eight primary metabolites with an unchanged position 4 in the heterocyclic ring were also detected and separated chromatographically. The detection limit for nafazatrom is 0.5 ng per spot and 5 ng/ml. The analytical error in the nanogram per millilitre range is less than 10%, low enough for pharmacokinetic studies and for plasma level monitoring in patients.

Animals↗
PubMed1984

The relation of P3b to prior events and future behavior.

A prediction paradigm was used to explore the relationship of the amplitude of the scalp-recorded event-related potential to the sequence of preceding signals and to preceding and subsequent behavior. P3b was found to be the only component which related systematically to prior sequence of signals. The CNV, P300E and Slow Wave were not affected by signal sequence. The P3b findings were the same for the emitted and evoked P3b, thus ruling out a sensory interpretation of the effect of signal sequence on P3b amplitude. Furthermore, it was found that signal sequence interacts with the subject's predictions in determining P3b amplitude. For signal discontinuations, P3b was large in amplitude regardless of what had been predicted. However, for signal continuations, P3b was small when continuations had been predicted, but large when discontinuations had been predicted. Finally, we found that for both correctly and incorrectly predicted signal continuations, larger P3bs were more likely than smaller P3bs to be followed by a prediction that the signal for the next trial would be different.

Adolescent↗
PubMed1984

Pharmacokinetics of the oral triazole antimycotic vibunazole in animals.

Methods of assay of the oral triazole antimycotic vibunazole (BAY n 7133) in body fluids by GLC, HPTLC and by a microbiological assay are described and compared. Bioassay data of vibunazole concentrations in mice and rats are lower than those of the chemical methods, probably due to a species-dependent difference in protein binding. The pharmacokinetics of vibunazole was studied after administration to mice, rats, rabbits, beagle dogs and rhesus monkeys. Peak concentrations of 14 to 16 mg/l were found in plasma of mice after oral administration of 25 mg/kg as an aqueous suspension. After the first oral dose the mean plasma half-life was 4.8 h. After the fifth dose, plasma levels were lower and declined with a half-life of 1.2 h which may indicate enzyme induction. Signs of enzyme induction after multiple oral doses were also seen in beagle dogs but not in rhesus monkeys. After intravenous administration to one beagle dog, vibunazole plasma half-life was 1.8 h. The absolute bioavailability of oral vibunazole in the dog was estimated to be about 70%.

Administration, Oral↗
PubMed1984

Retention time and concentration in human skin of bifonazole and clotrimazole.

The retention time and the extent of penetration in human skin of [14C] labelled bifonazole in comparison to [14C] labelled clotrimazole were investigated in 8 healthy volunteers. In the course of the investigation the backs of the volunteers were treated half with bifonazole, half with clotrimazole which remained on the skin for 24 h. From 24 to 168 h after the administration the skin was stripped with the tear-off strip technique. Three dermal layers of different depth were examined. The results of the examinations revealed, that the quantity of bifonazole that penetrated into the skin was more than twice as high as the quantity of clotrimazole. However, the half-lives and the mean retention times of bifonazole and clotrimazole were nearly similar to each other.

Administration, Topical↗
PubMed1983

The relationship between dose, pharmacokinetics, plasma-concentrations and antithrombotic effects of nafazatrom.

Nafazatrom is rapidly and almost completely absorbed after oral administration. However, the plasma levels of unchanged nafazatrom are very low, suggesting an extensive biotransformation during a first passage through the liver. The concentrations of nafazatrom in the plasma therefore, may only reflect indirectly the effective concentration at the receptor site. Concentrations, half-life and distribution of nafazatrom between aqueous and liquid compartments suggest that the cellular membrane may be the site of action.

Administration, Oral↗
PubMed1983

Pharmacokinetic studies following systemic and topical administration of [14C]bifonazole in man.

[14C]Bifonazole (1-[(4-Biphenylyl)-phenylmethyl]-1H-imidazole, Bay h 4502, Mycospor) was administered systemically (i.v.) and topically (dermally) in different formulations to a total of 17 volunteers. In the serum, the concentrations of total radioactivity and of the unchanged drug were determined by liquid scintillation counting techniques and by thin-layer densitometry, respectively. Urine and feces were collected and radioassayed. The extent of percutaneous absorption was calculated. In addition, distribution of the unchanged drug in the layers of the skin was studied radiometrically in three patients. After intravenous administration, bifonazole was eliminated from the serum largely in metabolized form. The half-lives of elimination of the radioactivity from the serum were approximately 7 and 42 h. Within 5 days 45% of the dose was excreted with the urine, and 39% with the feces. After topical application to healthy skin areas, under occlusive conditions, less than 1% of bifonazole was absorbed percutaneously from a 1% solution or cream, and the amount absorbed was excreted with the urine and the feces in approximately the same proportions as after i.v. administration. Following administration of the drug to inflamed skin, the proportion absorbed was 3 to 4% of the dose administered and thus higher than after application to normal skin. Studies on depth localization showed that the drug has a high capacity for skin penetration. Even in the lower layers of the epidermis, bifonazole was present in amounts several times as high as the minimum inhibitory concentrations for dermatophytes measured in vitro.

Administration, Topical↗
PubMed1982

Manipulation of event-related potential manifestations of information processing stages.

The timing of two event-related potential components was differentially affected by two experimental variables. The earlier component (NA) was affected by degradation of the stimuli and the later component (N2) by the nature of a classification task. The results support the hypothesis that NA and N2 reflect sequential stages of information processing, namely, pattern recognition and stimulus classification.

Action Potentials↗
PubMed1982

[The radiological and clinical features of Gardner's syndrome (author's transl)].

Gardner's syndrome, completely expressed, consists of a trio of familial polyposis of the colon, osteomas and mesenchymal tumours of the skin. Inheritence is autosomal dominant. In many patients with familial polyposis of the colon, only mesenchymal skin tumours or osteomas can be demonstrated. It is therefore possible that Gardner's syndrome and familial polyposis represent two extremities of a single disease which is characterised by marked variability in the expressivity of the gene. Gardner's syndrome has been considered a rare condition occurring in only about 8% of patients with familial polyposis. Amongst the 20 patients with colonic polyposis from eleven families, mesenchymal and/or osseous lesions were found in seventeen (85%). Osteomas of the mandible were shown particularly frequently by orthopantomography. Since polyposis of the colon tends to remain symptomless for many years, the finding of osteomas in the facial skeleton, or recurrent skin tumours in young patients, should lead to further investigation.

Adolescent↗
PubMed1982

Pharmacokinetic fundamentals of vaginal treatment with clotrimazole.

Absorption of clotrimazole after vaginal application was estimated to be between 3 and 10%. In order to investigate the fate of clotrimazole reaching systemic circulation, pharmacokinetic studies following oral and intravenous administration were carried out. The concentrations of clotrimazole in vaginal fluid and in blood plasma after vaginal application of 200 and 500 mg were determined using a specific assay by quantitative thin-layer chromatography. Fungicidal concentrations of clotrimazole in vaginal fluid up to 3 days after application of one vaginal tablet containing 500 mg were found. In contrast, clotrimazole plasma levels were lower than 0.01 micrograms/ml, demonstrating that clotrimazole is rapidly metabolized.

Carbon Radioisotopes↗