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R Neidlein

Publications and source records attributed to R Neidlein.

At least 37 records · Page 2Linked to original sources
PubMed1990

Pharmacokinetics of the partial beta-agonist doxaminol in dog.

The pharmacokinetic behaviour of doxaminol (N-methyl-N-(2-hydroxy-3-phenoxy-propyl)-11-(2-amino-ethyl)-6, 11-dihydrodibenz[b,e]oxepine, neutral fumarate; BM 10.188) was examined in dogs using peroral and intravenous application of the 14C-labelled drug. The maximum plasma concentration was reached 1 h after application, indicating a relatively quick absorption of doxaminol. Decrease of total radioactivity after intravenous and peroral application is characterized by two phases, the elimination half-lives being 1.33 and 1.55 h, respectively, and 24.05 and 21.05 h, respectively. The biological availability of doxaminol was ca. 60%. The plasma levels of the unchanged drug showed that doxaminol was very rapidly eliminated and metabolized. Within the examined period of 96 h, the elimination of doxaminol and its metabolites via urine and faeces amounted to 76.5% after intravenous application, and 44.1% of the applied dose after peroral application. The major amount of radioactivity is eliminated via faeces (61.5% and 31.2% of dose, respectively) while the elimination through urine is found to be 15.0 and 12.9% of the dose, respectively.

Administration, Oral↗
PubMed1989

[The disposition of bornaprine hydrochloride in the rat. 1. Pharmacokinetics: synthesis, plasma level and elimination].

The biliary elimination and plasma concentration-time course of radioactivity and unchanged compound of 2-phenyl-bicyclo-[2.2.1]- heptane-2-carboxlylic acid (4'-diethylamino-propyl)ester hydrochloride (bornaprine hydrochloride, Sormodren) were investigated after oral application in Wistar rats. The curves showed no obvious differences in their pharmacokinetic properties.

Animals↗
PubMed1989

[The disposition of bornaprine hydrochloride in the rat. 2. The metabolism of exo-epimers].

The biotransformation of an epimeric form of the anticholinergic drug exo-2-phenyl-bicyclo-[2.2.1.]-heptane-2-carboxylic acid (4'-diethylaminopropyl)ester hydrochloride (bornaprine hydrochloride, Sormodren) was investigated after oral application in male Wistar rats. Main metabolite of the exo-isomer in the feces was the hydroxylated and sulfate-conjugated product, substitution having occurred at C(5) of the bicyclic ring in exo-position. As further metabolites, the sulfate-conjugate in exo-position at C(6) and the N-desethyl derivatives of both were detectable.

Animals↗
PubMed1988

Synthesis of glucuronides of propafenone and 5-hydroxypropafenone by Sepharose-bound uridine 5'-diphosphoglucuronyltransferase.

Propafenone (Rytmonorm) and its in vivo metabolite 5-hydroxypropafenone were glucuronidated by agarose-bound uridine 5'-diphospho (UDP)-glucuronyltransferase from bovine liver in the presence of UDP-glucuronic acid. The identification of the synthesized glucuronides was based on the specific enzymatic hydrolysis, by mass spectrometry and by chromatographic comparison with isolated metabolites from dog and man. The glucuronidation of propafenone and 5-hydroxypropafenone followed Michaelis-Menten kinetics up to substrate concentration of 0.4 mmol/l (propafenone) and 0.3 mmol/l (5-hydroxypropafenone). The pH optima were 7.5 and 8.0, respectively. The reaction was linear up to 30 min and for a protein concentration between 1 and 5 mg per assay. 5-Hydroxypropafenone showed the best affinity with a Km value of 1.4 mmol/l, in contrast to 11.6 mmol/l for propafenone. The use of agarose-bound UDP-glucuronyltransferase offers the possibility to synthesize propafenone glucuronide and 5-hydroxypropafenone glucuronide which are needed for kinetic and pharmacological studies in man and animal.

Animals↗
PubMed1988

[Biotransformation of 4-oxa-5-exo-(N-methylcarbamoyloxy)-tricyclo-[5.2.1.0-2, 6endo] dec-8-en-3one in the rat].

The metabolism of the analgesic compound 4-oxa-5-exo-(N-methylcarbamoyloxy)-tricyclo-[5.2.1.0-2. 6endo]dec-8-en-3one (Lu 253) was investigated after oral application in male Wistar rats. From urine, faeces, bile, and plasma epoxidized, rearranged, and N-desmethylated metabolites were isolated. The main reaction was the epoxidation of the double bond. The structure of most of the biotransformation products was proved by synthetic compounds.

Animals↗
PubMed1988

[Pharmacokinetics of 4-oxa-5-exo-(N-methylcarbamoyloxy)-tricyclo- [5.2.1.0. 2,6-endo] dec-8-en-3-one in the rat].

Pharmacokinetics of 4-Oxa-5-exo-(N-methylcarbamoyloxy)-tricyclo- [5.2.1.0. 2,6endo]dec-8-en-3one in the Rat The pharmacokinetics of 4-oxa-5-exo-(N-methylcarbamoyloxy)-tricyclo- [5.2.1.0. 2,6endo]dec-8-en-3one (Lu 253) were investigated after oral application in male Wistar rats. The compound is extensively absorbed and mainly renally eliminated. Within 60 h, 63% of the activity is recovered in urine and faeces. After 12 h 27% of the activity is eliminated (application in polyethylene glycol). The highest total concentration of the activity in the plasma is found after 2 h, the highest of the unchanged drug is found after 1 h. The half-life is 2.9 h. The concentration in plasma is mathematically characterized by the parameters of a two-compartiment model and also independent of a model. Lu 253 is distributed in the whole organism, a maximum of activity is achieved 2 h after application. By whole-body autoradiography the entrance of the compound into liquor and an enduring accumulation in the frontal cavity is detected.

Analgesics↗
PubMed1987

[Biotransformation and pharmacokinetics of bamipine in rats. 1. biotransformation].

Biotransformation and Pharmacokinetics of Bamipine in Rats/1st Communication: Biotransformation studies. The metabolism of the antihistaminic N-phenyl-N-benzyl-4-amino-1-methylpiperidine (bamipine) was investigated after oral application in Wistar rats. The major metabolites in the urine were the ether glucuronides of N-p-hydroxy-phenyl-N-benzyl-4-amino-1-methylpiperidine and of N-p-hydroxyphenyl-N-benzyl-4-amino-piperidine. Unchanged drug was not detected. In vitro studies showed, in good correlation with in vivo studies, a oxidative demethylation of bamipin.

Animals↗
PubMed1987

[Biotransformation and pharmacokinetics of bamipine in rats. 2. Pharmacokinetics (P 2)].

After oral application pharmacokinetic parameters of N-phenyl-N-benzyl-4-amino-1-methylpiperidin (bamipine) were investigated. The curve of the plasma level is characterized by two maxima. If the first maximum is neglected, the calculated elimination half-life is 9.52 h, the invasion half-life 1.03 h. The first maximum is calculated as a lag-time (1.62 h). By whole-body radiography of the animal an accumulation of activity was determined in the glandular tissues behind the eye--beside the usual accumulation of activity in liver, spleen, kidney and lung.

Administration, Oral↗
PubMed1983

[Biotransformation und pharmacokinetics of beta-methyl[1,1'-biphenyl]-4-propanenitrile (LU 20884) in rats. Studies on biotransformation].

The metabolism of the antiphlogistic beta-methyl[1,1'-biphenyl]-4-propanenitrile (LU 20884) was investigated in urine after oral application in male Wistar-rats. Metabolite with the major share was alpha-hydroxy-4'-methoxy-alpha-methyl[1,1'-biphenyl]- 4-aceticacidmethylester, which could be identified by mass and 1H-NMR spectroscopy as derivative of diazomethane. Furthermore the following metabolites could be detected as 4'-methoxy-beta-methyl[1,1'-biphenyl]-4-propanoicmethylester and propanenitrile.

Animals↗
PubMed1983

[Biotransformation and pharmacokinetics of beta-methyl-(1,1'-biphenyl)-4-propanenitrile (LU 20,884) in rats. Spectroscopic studies].

Several compounds of comparison have been examined by their spectroscopic behavior in mass-, 1H-NMR- and IR-spectra of the antiphlogistic active beta-methyl[1,1'-biphenyl]-4-propanenitrile (LU 20,884). Characteristic fragments of alkyl-substituted biphenyls could be determined as well as the localisation of hydroxylated products in 1H-NMR-spectra.

Animals↗
PubMed1983

[Biotransformation and pharmacokinetics of beta-methyl-(1,1'-biphenyl)-4-propanenitrile (LU 20884) in rats. Studies on pharmacokinetics].

After oral application in Wistar rats the pharmacokinetic properties of beta-methyl[1,1'-biphenyl]-4-propanenitrile (LU 20884) were investigated. The compound is extensively absorbed, a maximum amount of 8.9% being eliminated as unchanged drug. The half-life in plasma is 22.7 h; the highest concentration in plasma is reached after 6.85 h. The maximum of the primary product is achieved after 4 h which substantiates its intensive and fast rate of metabolism. The distribution of LU 20884 is to be seen in the whole organism. An enrichment of activity is to be found in liver and kidney. The lowest concentration can be detected in brain. The elimination takes place almost equally in urine (44.7%) and feces (41.3%). The total excretion of the administered activity is 86.0% after 96 h; 1.8% of the activity still remains in the organism.

Animals↗
PubMed1982

[Biotransformation and pharmacokinetics of mesoionic didehydro-4-methyl-5-phenyl-1,3,4-thiadiazolidine-2-thione (LU 2443). Studies on its biotransformation in rats].

The metabolism of the antiepileptic mesoionic didehydro-4-methyl-5-phenyl-1,3,4-thiadiazolidine-2-thione (LU 2443) was investigated after p.o. application in rats. The main metabolite was benzoic acid, besides the unchanged material and hippuric acid the spasmodically compounds N-methyl-benzamide and mesionic didehydro-4-methyl-5-phenyl-1,3,4-thiadiazolidine-2-one were detectable. In-vitro experiments could be demonstrated that LU 2443 was not demethylated by biochemical oxidation, and LU 2443 was also very stable against metabolizing influences by enteric bacteria.

Animals↗
PubMed1982

[Biotransformation and pharmacokinetics of mesionic didehydro-4-methyl-5-phenyl-1,3,4-thiadiazolidine-2-thione (LU 2443). Studies on the pharmacokinetics in rats].

After p.o. application in rats the pharmacokinetic properties of the mesionic dihydro-4-methyl-5-phenyl-1,3,4-thiadiazolidine-2-thione (LU 2443) were examined. The compound is extensively absorbed, in the maximum 18% are eliminated unabsorbed. The half-time of the activity in plasma is 13.17 h, the highest concentration in plasma after p.o. application as a solution of polyethyleneglycol is reached after 5.09 h. The elimination is mainly renal--namely 61.9%, 28.7% are eliminated with the faeces. After 96 h 90.6% of the applicated activity was eliminated. The distribution of LU 2443 was in the whole organism; entrance of the compound into liquor was proven. By radiography of the total animal a transient accumulation of LU 2443 and its metabolites in liver and kidney was determined; besides, a considerable concentration of activity in the suprarenal medulla was found.

Administration, Oral↗