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Biomedical subjects

F Leuschner

Publications and source records attributed to F Leuschner.

At least 19 recordsLinked to original sources
PubMed1992

[Pharmacokinetic aspects of a combination of metoclopramide and paracetamol. Results of a human kinetic study and consequences for migraine patients].

An open trial was carried out in eight healthy male and female volunteers to examine the bioavailability as well as the main kinetic parameters of Migränerton (metoclopramide and paracetamol; CAS 364-64-5 and CAS 103-90-2, resp). in comparison with reliable literature data. The results reported here clearly show that the absorption of both active ingredients from the fixed combination is complete and that therapeutically relevant plasma concentrations are achieved within 30 min. Bioavailability as well as tmax, t1/2, and time-lag are comparable with data resulting from reliable and internationally acknowledged kinetic studies. The fixed combination was shown to be kinetically compatible with regard to all parameters determined for metoclopramide and paracetamol.

Acetaminophen↗
PubMed1991

Toxicokinetic aspects of chronic cyanide exposure in the rat.

Rats received 40, 80 and 160 mg KCN/kg body wt./24 h in the drinking water for 13 weeks. Fairly constant dose-related cyanide and thiocyanate levels were measured in blood, plasma and urine during the exposure. Blood cyanide concentrations were in the range of 16.0-25.5 nmol CN-/ml blood, thiocyanate concentrations in the range of 341-877 nmol SCN-/ml plasma following continuous administration of the maximum tolerated dose-level of 160 mg/kg body wt/24 h. The results suggest that continuous 13-week maximum tolerated cyanide exposure does not lead to saturation of cyanide detoxification pathways.

Administration, Oral↗
PubMed1989

Toxicity of 8-methoxypsoralen in cynomolgous monkeys (Macaca fascicularis).

Male and female cynomolgous monkeys were administered 0, 2, 6 or 18 mg/kg 8-methoxypsoralen (8-MOP) 3 times a week orally for 26 consecutive weeks. Dose-dependent emesis was the most sensitive indicator of 8-MOP toxicity. The lowest dose to elicit emesis was 3 x 6 mg/kg/week of 8-MOP. Among the histological findings proliferation of Kupffer cells was the only recurring observation. However, these finding as well as some hematological and serum electrolyte changes lacked a dose-response relationship. In the highest dosage group one female monkey was found in moribund condition on the 39th day of the study and was killed. Histopathological evidence indicated beginning shock as the cause of the rapidly deteriorating health of the monkey. Similar to effects in man and rats, 8-MOP displayed nonlinear pharmacokinetics in the cynomolgous monkey, saturation occurring between 3 x 2 and 3 x 6 mg/kg/week. Increased clearance of 8-MOP in the lowest dosage group after 26 test weeks was attributed to a combination of enzyme induction and saturable first pass effect. Since the plasma profile of 8-MOP at the lowest dose (3 x 2 mg/kg/week) in cynomolgous monkeys closely resembles that in humans after therapeutic doses (0.4-0.6 mg/kg) and because of other similarities (vomiting as earliest sign of toxicity, saturable first pass effect), it is reasonable to assume that chronic toxicity of 8-MOP as defined in this study is quite predictive for man.

Animals↗
PubMed1987

Embryotoxicity of sex steroidal hormone combinations in nonhuman primates: I. Norethisterone acetate + ethinylestradiol and progesterone + estradiol benzoate (Macaca mulatta, Macaca fascicularis, and Papio cynocephalus).

Two sex steroid hormone combinations which have been used clinically as tests for detection of early pregnancy were examined for embryotoxic effects in macaques and baboons. Norethisterone acetate and ethinyl estradiol (NEA + EE) were orally administered to rhesus and cynomolgus monkeys and baboons at dosages ranging from one to 1,000 times the human dose equivalent (HDE) during days 20-50 of pregnancy. Progesterone and estradiol benzoate (P + EB) were delivered by two to six intramuscular injections to rhesus and cynomolgus monkeys between gestational days 20 and 35 at 0.1-25 X HDE. Fetuses were examined following cesarean section at 100 +/- 2 days (NEA + EE) or at term (P + EB). The results showed increased embryolethality over controls at 100-1,000 X HDE (NEA + EE) and at 10 and 25 X HDE (P + EB). Besides growth retardation, isolated cases of minor nongenital malformations were observed only in cynomolgus monkeys following treatment with both hormone combinations mainly at embryolethal dose levels and were considered spontaneous in nature. Virilization of female cynomolgus fetuses following NEA + EE treatment was manifested as two cases of clitoral enlargement in the 300 X HDE group and two cases of increased anogenital distance with reduced vaginal opening in the 1,000 X HDE group. The highest dose of NEA + EE was also maternally toxic, as two maternal deaths occurred at the end of the treatment period. One dead female cynomolgus fetus exposed to P + EB (10 X HDE) also exhibited masculinized external genitalia.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1987

Embryotoxicity of sex steroidal hormones in nonhuman primates: II. Hydroxyprogesterone caproate, estradiol valerate.

Two sex steroid compounds which have been used clinically for parenteral supportive therapy of pregnancy were examined for embryotoxic effects in rhesus and cynomolgus macaques. Hydroxyprogesterone caproate (HPC) alone or in combination with estradiol valerate (EV) were administered intramuscularly (i.m.) to pregnant monkeys at 7-day intervals between 20 and 146 days of gestation and fetuses were examined following cesarean section at 150 +/- 2 days. HPC alone was tested in both species at doses ranging from 0.01 X to 10 X the human dose equivalent (HDE); only rhesus monkeys were exposed to the HPC + EV combination at 0.1 X to 10 X HDE. Total embryolethality resulted following the administration of HPC alone and combined with EV at 1 X and 10 X HDE in rhesus monkeys; the level of abortions in cynomolgus monkeys exposed to HPC (0.1 X to 1 X HDE) was comparable to controls. A small number of nonspecific malformations and developmental variations observed in cynomolgus fetuses after HPC exposure were considered to be incidental findings. No anomalies were found in surviving rhesus monkey fetuses treated with HPC + EV. The results indicate that long-term in utero exposure to the progestin, HPC, alone or in combination with EV in rhesus and cynomolgus monkeys, is embryolethal but not teratogenic at doses up to ten times the human therapeutic dose.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1987

Test guideline. Behavioral toxicity testing in animal experiments according to section 9, para. 1, No. 2 of the Chemicals Act (Chemikaliengesetz) of the Federal Republic of Germany.

The German Chemicals Act requires that chemicals are tested for behavioral toxicity at stage 2 of the testing procedure, i.e. if more than 1000 annual tons are produced. For this purpose a guideline was developed according to which data on behavioral toxicity are to be collected, which are based on cageside observations during longterm exposure. The protocol covers outer appearance, as well as motor, sensory, autonomic and central nervous system functions. Data are to be reported in tabular form and should be evaluated by taking all aspects of the toxicological profile into account.

Animals↗
PubMed1985

[Toxicologic studies with thymostimulin].

Thymostimulin (Tp-1 Serono) was tested toxicological in rats and monkeys during 6 weeks of repeated administration. Corresponding to the therapeutic use intended in man the substance was given to rats and monkeys intramuscularly in dosages of 10 or 100 mg/kg b.w. and due to technical reasons subcutaneously in a dosage of 1000 mg/kg b.w. No substance-related effects, either systemic or local, were observed in the monkeys. After treatment with the high dose level (1000 mg/kg b.w. s.c.) the rats exhibited inflammatory changes in the region of the injection sites.

Animals↗
PubMed1977

[Compound with bronchospasmolytical activity from the chemical class of beta-phenylethyl-aminoalkyl-xanthines (author's transl)].

1. 7-(3-[2-(3,5-Dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, D 1959, Bronchospasmin) was developed as a bronchospasmolytic agent from the structure class of the phenylethyl-aminoalkyl-xanthines. 2. The pharmacological effects characterize reproterol as a bronchospasmolytic with preferential impact on the adrenergic beta2-receptors. 3. In the therapeutic dose range, reproterol stands out because of its nearly non-existent cardiovascular or central nervous side effects. Effects of over and above pharmacodynamically effective doses as well as toxic ones may be reversed with beta1-receptor blockers.

Adrenergic beta-Agonists↗
PubMed1977

[Toxicological investigation of reproterol (author's transl)].

Only slight toxicity of 7-(3-[2-(3,5-dihydroxyphenyl-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, Bronchospasmin) was shown in the examination of acute, subacute and chronic trials on various animal species with different modes of application. Slight side-effects noted with high toxically active dosages correspond with those of other well-known beta-sympathicomimetics. No influence on the pre-,peri- and postnatal development could be proven with doses tolerated by the parent animals.

Abnormalities, Drug-Induced↗
PubMed1977

[Toxicological study on piprozoline (author's transl)].

The compatibility of ethyl (Z)-(3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (piprozoline, Gö 919, Probilin) was tested orally in rats and intragastrically in dogs for 6 months. Moreover, the effect of the substance was studied on pregnant rats and rabbits and their foetuses after intragastric administration and on the fertility and breeding capacity of rats after oral application. In the course of the chronic experiments, in the highest dosage group of rats a slight sedation and a decrease of body weight gain and food intake could be observed. The female animals showed an enlargement of the adrenal glands. A small hyperemesis was noted in the highest dosage group of dogs. Subtoxic doses applied to rats and rabbits during gestation did not induce malformations in the newborns. Even treatment with large doses did not influence fertility and breeding capacity.

Animals↗
PubMed1977

[Toxicological studies on Etozolin (author's transl)].

The tolerance of ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (etozolin, Gö 687, Elkapin) has been investigated over 18 months after oral administration in rats and over 1i months after intragastric application in dogs. Further the influence of the compound on pregnant animals and their fetuses after intragastric application has been investigated in rats and rabbits. The investigation of the influence on fertility and breeding capacity as well as on the peri- and postnatal development was carried out in rats after peroral administration. In the course of the chronic experiments a dose related increase of the excretion of fluid and electrolytes was observed. Side-effects, which mainly occurred during the last weeks of the experiment in the highest dosage group, were most probably due to the exhaustion of the fluid and especially of the electrolyte reserves of the animals. The experiments in rats and rabbits did not yield any findings indicating teratogenic properties. Fertility and breeding capacity were likewise not influenced by etozolin. An influence on the peri- and postnatal development could be demonstrated only in the toxic dose range.

Administration, Oral↗