摘要:

A method for measuring thioxanthenes at therapeutic levels in plasma, based on the measurement of the fluorescence of the oxidized drugs, has been developed. The method permits estimation of about 3 ng of the drug. The disappearance of the drug from the plasma was followed after intravenous administration to rabbits and oral administration of a therapeutic dose to human volunteers. N‐demethylthiothixene is identified as a metabolite of thiothixene in ma

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00591.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Brain tissue is extracted with perchloric acid. The pH of the extract is adjusted to 2.5 and passed through a Dowex 50 W‐X4 column. 5‐Hydroxy‐3‐indole acetic acid is eluted with 60 % aqueous methanol, and then 5‐hydroxytryp‐tophan is eluted with 0.1 M phosphate buffer, pH 6.5. Fluorometric assays are performed according to the method for 5‐hydroxytryptamine described by Andéen&Magnusson (1967). The results are satisfactory with regard to reproducibility, recovery, specificity, and sensitivity. If the above procedure is combined with that published by Atack&Magnusson (1970), then 7 different compounds can be estimated after a single co

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00592.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

In normal human subjects multiple dose trial with an initial dose of 400 mg doxycycline and subsequent doses of 200 mg every 24 hours gave average minimum serum concentrations of between 1 and 2 μg doxycycline/ml serum. The average urine concentrations varied between 100 and 200 μg doxycycline/ml urine, and 42 per cent of the drug administered was excreted in the urine in an active form. The average renal clearance of doxycycline determined over 96 hours was 28 ml/min. In a single dose trial with 200 mg doxycycline, an 8‐hour renal clearance of doxycycline was found to be 13 per cent of the creatinine clearance, and the serum half‐life period was found to be 11.6 hours. Microbiological assay was used for all determinations of doxycycline in the serum and urine. Thein vitrosensitivity of 211 urinary tract pathogens to doxycycline and oxytetra‐cycline was investigated in order to determine the minimum inhibitory concentration (MIC). The strains, which originated from patients with chronic urinary tract infections, were as a whole only slightly sensitive to the two tetracyclines. Compared with oxytetracycline, doxycycline, assessed at the MIC‐level, showed a higher bacteriostatic effectin vitro, especially against gram‐posit

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00593.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The effects of stimulation of the adrenergic α‐ and β‐receptors in muscle from the antrum and fundus of the rabbit stomach have been studied. The muscular activity was markedly different in preparations from the two parts. In the muscle from the antrum rhythmic contractions generally occurred, while alterations in the tone were small and infrequent. In the muscle from the fundus, rhythmic contractions were rarely seen, but considerable variations in tone occurred in response to drugs. β‐receptor stimulation invariably gave inhibitory effects, but the effect of α‐receptor stimulation in longitudinal and circular antrum strips, and in longitudinal fundus strips, depended on the existing muscular activity when the drug was added, high activity favouring inhibitory effects and low activity favouring excitatory effects. In a few antrum strips low concentrations of α‐adrenergic agents increased the frequency of the rhythmic contractions while higher concentrations inhibited them. In circular strips from the fundus α‐receptor stimulation gave only excitatory responses. The effect of the adrenergic agents were apparently due to a direct influence on the muscle, as the quality of the responses was unaffected by pretreatment with atropine, hexamethonium and tetrodotoxin, by the presence or absence of mucosa, or by cold sto

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00594.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The metabolism of flupenthixol decanoate administered in viscoleo® by intramuscular or subcutaneous injection has been studied by thin‐layer chromatographic techniques after extraction of urine, faeces and organs from dogs and rats. Since only minute amounts of the compound itself were detected in the organs and a high hydrolytic activity of blood and organs was demonstrated byin vitroexperiments, it was concluded that the compound is hydrolyzed in the organism. The flupenthixol thus formed was found to be metabolized by sulphoxidation and by dealkylation in the side chain following the same pattern as that previously shown for flupenthixol. The neuroleptic effect seen in the pharmacological studies is presumably due to flupenthixol, since this is quantitatively by far the most important substance found in brain extracts. In order to study the depot effect of the preparation, blood levels and excretion were followed after administration of the3H‐labelled compound. These studies indicated, that a sustained release of drug from a depot was obtained. The presence of a relatively limited depot was demonstr

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00595.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

The isolated perfused rat liver was used in order to study the metabolism of the tricyclic antidepressant drug, desmethylimipramine (DMI), which is metabolized by oxidation and subsequent conjugation. DMI labelled with tritium in a position in which it is not eliminated by metabolism, was used. Extraction procedures were developed which allowed a separation of DMI and its hydroxyl‐ated and conjugated metabolites. DMI and its metabolites were measured in perfusate plasma, bile and liver. DMI disappeared quickly from the plasma and reappeared in high concentrations in liver and bile. The drug was highly bound to proteins in perfusate plasma, while the conjugated metabolites were not bound at all. The red blood corpuscles contained approximately ten times higher concentrations of DMI than perfusate plasma but no conjugated metabolites. Only small amounts of unconjugated hydroxylated metabolites were found in perfusate plasma, liver and bile in contrast to the conjugated metabolites which occurred in considerable amounts in perfusate plasma and bile. DMI was bound to the microsomal fraction of the liver cell. The conjugated metabolites appeared mainly in the cytoplasm of the liver cel

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00596.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY

摘要:

Biotransformation of methyl mercuric chloride in the mouse was followed by the specific determination of inorganic mercury after a single injection of the organomercurial. Inorganic mercury was detected in the blood, brain, liver, kidney, spleen and in the intestinal cells. Inorganic mercury was also found in the bile and faeces. The results indicate a role of biotransformation in the excretion of mercury after the injection of methyl mercuric salts. Inorganic mercury was preferentially excreted in the faeces. Differences in pharmacokinetics of methyl mercuric salts between rats and mice have been discussed with regard to differences in biliary excretion and enterohepatic circulation. The importance of taking into account species differences in the evaluation of toxic hazards of methyl mercuric salts has thus been demonstrated.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1971.tb00597.x

出版商:Blackwell Publishing Ltd    

年代:1971

数据来源: WILEY