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Biomedical subjects

A Zimmer

Publications and source records attributed to A Zimmer.

At least 109 records · Page 6Linked to original sources
PubMed1981

[Human pharmacokinetics of AR-L 115 BS (author's transl)].

Following i.v. administration of 0.7 mg of 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS)/kg (bolus) the terminal plasma elimination half-life (beta-phase) was in the range of 50 min. A fast absorption of the patent compound could be observed after oral administration of 50, 75, 10 and 150 mg AR-L 115 BS (solution). The AR-L 115 BS plasma level behaviour was characterised by a fast elimination of the parent compound.

Administration, Oral↗
PubMed1979

[Pharmacokinetics of fominoben-HCl in the dog and the rabbit (author's transl)].

The pharmacokinetics of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)-methyl]-aminomethyl)benzanilide-hydrochloride (P-B 89 Cl, fominoben-HCl, Noleptan) was studied in dog and rabbit following a dose of 3 mg/kg on i.v. and p.o. administration of the 44C-labelled compound. Absorption: The compound is absorbed fast in the dog and very fast in the rabbit. Practically the entire dose is absorbed by the two species. Maximum levels in blood: dog 0.5 microgram/ml, rabbit 0.8 microgram/ml, in the plasma: dog 0.6 microgram/ml, rabbit 1.2 microgram/ml at 1--2 h p.a. and 15--30 min p.a. Elimination: The elimination from blood and plasma proceeds biphasically. 1st half-life: 1--2 h, 2nd half-life: 19--27 h (higher values for the rabbit). The dog eliminates preponderantly via the bile with the faeces, the rabbit via the kidneys: Dog: 19% in urine and 63% in faeces, rabbit 79% in urine and 16% in faeces, measured up to 96 h p.a. One rabbit excreted 70% via the urine up to 7 h p.a. The half-lives of urinary elimination are very well comparable with the figures for plasma. Biotransformation: Plasma (maximum level): Dog: Visible amounts of parent compound (M0), Rabbit: Traces M0, much M2. Urine (0--24 h p.a.): Dog: Traces: M0, Rabbit: Traces M0, much M2.

Animals↗
PubMed1978

Pharmacokinetics and metabolite-pattern of 8-methoxypsoralen in man following oral administration as compared to the pharmacokinetics in rat and dog.

Following oral administration of 14C labelled 8-methoxypsoralen (8-MOP) in man the plasma level course, the metabolite-patterns and the elimination of the parent compound and its metabolites have been investigated. Additionally the results discovered have been compared with the data of pharmacokinetics on dog and rat. In man and rat the plasma protein binding of 8-MOP has been determined. Maximal levels of the total radioactivity in the plasma were achieved 2 h after dosing. At this time 8-MOP represents 50% of the radioactivity in the plasma. The plasma protein binding in vitro of 14C 8-MOP valued from 88% to 91% in man, and between 75% and 83% in the rat. Urinary elimination of the total radioactivity as a measure of the extent of absorption varies greatly and depends on the therapeutic formulation being employed. Following the administration of the solution 74% is recovered within 48 h. Faecal elimination of the total radioactivity reached 14% within 3 days. The metabolite-pattern does not show the unchanged 14C 8-MOP. Several polar metabolites occur in the urine among which biochemical conjugates have been recognized. Only polar metabolites are observable in the faeces from which the radioactivity is incompletely extractable. From a comparison of the metabolite profiles, the rat as well as the dog seem to be a useful animal species for experimental investigations with 8-MOP.

Administration, Oral↗
PubMed1978

[Studies on the biotransformation of fominoben-HCl in man (author's transl)].

The biotransformation of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]aminomethyl)benzanilide hydrochloride (fominoben-HCl, PB 89 Cl, Noleptan) was investigated in man. The most substantial metabolites were quantified. The metabolite patterns of fominoben in urine and plasma are compared. Fominoben, is rapidly and extensively metabolized to many metabolites. At the time of the maximum plasma level. 2 h after an oral dose of 160 mg of 14C-PB 89 Cl, only 1.5% of the plasma radioactivity can be measured as the unchanged initial compound. No parent compound can be found in the urine, only in the stool some traces of fominoben can be detected. The biotransformation can be characterized by four main pathways: 1. cleavage reactions, 2. hydroxylations, 3. cyclisations, 4. conjugations. The reactions 1--3 proceed as well simultaneously as successively.

Adult↗
PubMed1978

[Pharmacokinetic studies on fluoro-alpha-acetyl-digoxin (author's transl)].

Pharmacokinetic studies with a new cardiac glycoside 3H-fluoro-alpha-acetyldigoxin were carried out in humans. The absorption of the drug is 91%. The half-life of tritium label in plasma was 25 h i.v. and 35 h p.o. 73% of the administered radioactivity were excreted after i.v. and 52% after oral administration within 84 h. More than 60% of the radioactivity in the urine could be extracted with chloroform. This fraction corresponded mainly to 3H-fluorodigoxin in the thin-layger chromatogram. Protein binding was 27% using therapeutic concentrations.

Administration, Oral↗
PubMed1977

[Dependence of lactate and heart rate in ergometer-, running- and swimming stress and its use for the preparation of individual conditioning programs for patients with myocardial infarct in rehabilitation phase III].

The dependence of the heart rate of 25 patients between 6th and 12th month after myocardial infarction on the lactate deflection during bicycle ergometry was compared with values being measured in physical conditioning in gymnasium and in indoor swimming-bath. There were found congruent statements in all three types of stress. The immediate comparison of patients undergoing rehabilitation who realized a gymnasium and swimming program simultaneously, showed no differences in lactate deflection and heart rate, too. So heart rates of equal level signal the production of equal metabolic training irritations in the three types of stress being tested. Moreover it was to be ascertained that the optimum intensity of the physical conditioning of patients with myocardial infarction is reached with a lactate deflection of 2,5 to 4,0 muMol/1, appropriate to a heart rate of 104 to 120 beats every minute resp. an efficiency of 70% of the submaximum aerobic capacity.

Conditioning, Psychological↗
PubMed1977

[Dependence of lactate on pulse rate, performance and cardiac volume performance quotient in rehabilitated myocardial infarct patients during bicycle ergometry].

All males of the district Cottbus who suffered from an acute myocardial infarction between 1 June 1973 and 30 June 1974 and survived the first rehabilitation phase of a definite myocardial infarction were included in the study. Their arterial lactate level, the oxygen intake, the heart rate and heart size were determined by means of standardized ergometry and radiology. Patients who had performed a rehabilitation training programme showed a higher efficiency and equal values of lactate level and heart rate compared with the patients without training programme. A close correlation also existed between lactate level and heart rate. There was no dependence on the age of the patient or the degree of heart insufficiency. These results allow to conclude that the lactate level can be used for the determination of the training intensity of patients after an acute myocardial infarction.

Aged↗
PubMed1976

Investigation of the pharmacodynamics and pharmacokinetics of 2-(2,4-dimethoxyphenyl)-Imidazo-(4,5-b)-pyridine hydrochloride (AR-L 57 CL) in man.

AR-L 57 CL is an imidazole derivative which has been shown in animal studies to have a pronounced positive inotropic effect. This effect and the pharmacokinetics of AR-L 57 CL have been investigated by non-invasive methods in 8 healthy volunteers. After a single intravenous dose of 200 mg, administered as part of Phase 1 of the clinical studies, AR-L 57 CL plasma concentrations were measured by fluorimetry at intervals for up to one hour. Its inotropic action on the heart was demonstrated by changes in the systolic time intervals: QS2 = duration of electro-mechanical systole; PEP = pre-ejection period; LVET = left ventricular ejection time. The decrease in plasma concentration could be expressed in terms of an open two-compartment pharmacokinetic model. The shorter elimination phase had a t1/2 of 4 min and the longer a t1/2 of 30 min. Immediately after injection, QS2 and PEP (corrected for heart rate) as well as PEP/LVET (independent of heart rate) decreased considerably. They had returned to normal by 22 min after injection. The plasma concentrations of AR-L 57 CL of 2 - 5 mug-equivalents/ml showed a highly significant correlation with the decrease in systolic time intervals. Both systolic and diastolic blood pressure rose briefly after injection. The AV conduction time fell initially and the heart-rate increased briefly. Thus AR-L 57 CL was shown to be a short acting drug with a high degree of positive inotropic action. It did not cause bradycardia or increase atrioventricular transmission time and appeared to be easily controllable.

Adult↗
PubMed1976

[Pharmacokinetics and metabolite pattern of clenbuterol in the rat].

Pharmacokinetics and metabolite pattern of the beta-sympathomimetic 4-amino-alpha-[tert.-butylamino)methyl]-3,5-dichlorobenzyl alcohol hydrochloride (clenbuterol, NAB 365) have been investigated in the rat. After a single i.v. dose of 2 mg/kg 14C-NAB 365 up to 10 min p.a. the blood level falls very steeply and 15 min p.a. there is an increase to be observed. A maximum blood level of 0.85 mug eq. NAB 365/ml is achieved. Then a biphasic elimination of radioactivity from the blood occurs. After a single oral dose of 2 mg/kg the maximum blood level of 0.5 mug/ml is attained 2 h p.a. Again a biphasic elimination occurs. 26 h is the half-life of the slower of two elimination processes for i.v. and p.o. administration, respectively. Elimination predominantly takes place via the kidneys. After i.v. administration 85% and after p.o. administration 80% of the radioactivity applied are eliminated in urine and faeces. The main portion of radioactivity had been eliminated by 48 h p.a. As can be seen from the urinary radioactivity absorption is complete. Following i.v. dosing the excretion is slightly faster than after p.o. administration. Whole-body autoradiography and the distribution of radioactivity in the organs show a relatively slow absorption after p.o. dosing. In the pregnant mouse the placenta barrier is passed but the fetuses contain far less radioactivity than the mother animal. Clenbuterol is metabolized in the rat. 70% of the radioactivity represents the unchanged parent compound in urine (38% of the administered radioactivity). 8 metabolites have been established in urine (extracts). Faeces radioactivity mainly contains unchanged clenbuterol and only traces of metabolites. The metabolite pattern of the maximum plasma level (2 h after p.o. administration) and the metabolite pattern of the collected urines are identical. 38% of the administered radioactivity represent unchanged NAB 365 in the urine, whereas there are 45% in the plasma.

Administration, Oral↗
PubMed1976

[Comparison of the pharmacokinetic profiles of clenbuterol in rat and dog during toxicological studies (author's transl)].

The pharmacokinetics of the beta-sympathomimetic 4-amino-alpha-[(tert.-butylamino)methyl]-3,5-dichlorobenzyl alcohol hydrochloride (clenbuterol, NAB 365) have been investigated in two animal species during the chronic toxicological studies after single and multiple dosing. After oral administration of 2.5 mg/kg (dog) and 5 mg/kg (rat) the plasma levels showed significant differences. Moreover, a marked sex difference was to be seen in the plasma levels of the rat. The excretion, established only in the dog, showed no difference after single or multiple administration. The elimination occurs predominantly via the kidneys, and the main urinary elimination product is the unchanged clenbuterol. Each of the 8 metabolites is formed only in minor quantities. The biotransformation is not altered by long-term administration. The differences in the plasma levels that are observed with larger doses can be explained by the biological adaptation of the gastrointestinal tract during multiple administration.

Animals↗
PubMed1976

[Pharmacokinetics and metabolism of trazodone in man (author's transl)].

After intravenous, intramuscular and oral administration of 25 mg 14C-labelled 2-(3-[4-(m-chlorophenyl)-1-piperazinyl]-propyl)-s-triazolo[4,3-a]pyridin-3-(2H)-one-hydrochloride (trazodone), plasma levels, elimination and metabolite pattern in plasma and urine were investigated. The plasma levels after all routes of administration are almost identical. The absorption of the compound is fast and complete. The elimination of radioactivity occurs in a biphasic manner with a half-life of 1 h for the earlier and 13 h for the second phase, no matter what application route had been chosen. The comparison of the plasma levels of fasted and non-fasted subjects shows a shift of the plasma maximum from 1.5 to 2.5 h following administration and a decrease in the maximum level of 30%. The radioactivity is excreted predominantly by renal processes (70-75% within 72 h). The main product in plasma is unchanged trazodone, whereas in urine it is found only in minute amounts. The radioactivity in urine is represented by conjugates that had formed after hydroxylation on the chlorophenyl residue (20%), by a dihydrodiol-metabolite of trazodone (15%) and by a carboxylic acid originating from oxidative cleavage of the parent compound (35%).

Administration, Oral↗