摘要:

Abstract:The pharmacokinetics of theophylline after oral administration in tablet (Oxyphyllin®) or solution (Teovent®) form was determined in 22 children 0.6–16 years of age. Four of these children also received intravenous theophylline. The absorption of theophylline both from the tablets and from the solution was rapid (mean half‐time 14.3 and 16.1 min., respectively) and almost complete. The youngest children (2–8 years) given tablets had a significantly shorter half‐time of elimination and a higher total plasma clearance than children aged 9–16 years. Adverse effects during treatment with the oral solution were studied in another 19 children. Medication was stopped by the parents of two children because of the unpleasant taste. Gastrointestinal disturbances were frequent but not serious enough to cause discontinuation of treatment. Simulations based on obtained pharmacokinetic data showed that in the average child below nine years of age oral theophylline, 6–8 mg/kg three times daily, would give plasma levels between 10 and 20 μg/ml (55–110 μmol/l) for about 60–70% of the day. A dose of 6 mg/kg four times daily would achieve such concentrations during almost 24 hrs of the day. In the average child aged 9–16 years a reduced dose of about 5–6 mg/kg three times daily would suffice to produce plasma levels of 10–20 μg/ml owing to the slower elimination of the drug in this age group. Individual titration of the dose is necessary for optimal treatment with theo

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01044.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:In isolated human crural veins studiedin vitropinacidil (0.038–380 μM) caused a concentration‐related inhibition of noradrenaline, 18 μM (NA) and 127 mM K+‐induced contractions. Pinacidil was more potent in inhibiting the NA‐contraction than that induced by K+, whereas the reverse was seen for nifedipine. At the highest concentrations greater inhibitions of the NA‐induced contractions could be obtained with pinacidil than with nifedipine. The inhibitory effect of pinacidil on the K+‐induced contractions was eliminated during a 1 hr wash‐out period. In contrast to this, the inhibitory effect of nifedipine could not be eliminated during 4 hrs repeated wash‐out. Pinacidil was completely devoid of inhibitory effect on45Ca net influx in rat aorta, whereas nifedipine caused a significant reduction of influx. The results indicate that both pinacidil and nifedipine are effective vasodilatators in human vessels. Pinacidil seems to be more effective in NA‐induced contractions than does nifedipine. The mechanism of action of pinacidil cannot be attributed to an inhibitory effect on cel

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01045.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Vitamin A and its analogues show the ability to prevent malignant cell transformation on induction with different carcinogens, such as nitrosamines. Cyclic GMP has been proposed as a positive modulator of malignant cell growth and the cGMP‐forming enzyme guanylate cyclase is strongly stimulated by e.g. nitrosamines. In this study, we found that retinylacetate and retinal were very potent inhibitors of the stimulated guanylate cyclase. When a series of structurally different retinoids were tested in the same system, a wide range of inhibitory activity on guanylate cyclase was found for the different retinoids with some being completely ineffective. The most potent inhibitor was retinylacetate. Furthermore, the inhibitory profile of the retinoids on the guanylate cyclase did not seem to correlate to theirin vivoactivity as antineoplastic agents, as described in the literature. We therefore conclude that there does not exist a general connection between the anticancer activity and the guanylate cyclase inhibition of the retinoids. However, it can not be excluded that the guanylate cyclase inhibition might be of importance for the antineoplastic activity for some of the retinoid

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01046.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:We describe the precision and accuracy of a liquid chromatographic method, which uses internal standards, 6‐fluoroserotonin and 5‐hydroxyindolecarboxylic acid, in quantitating serotonin and 5‐hydroxyindoleacetic acid in human cerebrospinal fluid, plasma and urine. In addition, 5‐hydroxytryptophan is measured in the cerebrospinal fluid. The limit of sensitivity of this method is 0.1 pmol/injection, the peak height/concentration ratio is linear in the concentration range of 0.1 pmol to 50 μmol/injection, and the coefficient of variation is of the order of 15% at the limit of sensitivity and below 10% at amounts above 0.5 pmol/injection. No endogenous monoamines or their metabolites interfere with the quantitation of the substances of interest in the body fluids

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01047.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The placental transfer of the non‐metabolisable α‐aminoisobutyric acid was studied by means of a perfusion technique in pregnant guinea‐pigs given the commercial chlorobiphenyl preparation, Clophen A50 (C‐A50) or pure 2,2′,4,4′,5,5′‐hexachlorobiphenyl (HCB), during different periods of gestation. It was shown that a total dose of 30 mg of HCB given during the latter part of gestation (day 45 to 61) decreased amino acid transport, while 30 mg of C‐A50 did not. At a dose of 30 mg daily given from day 28 to day 61, again only HCB decreased the amino acid transfer. An amount of 60 mg C‐A50 was required to reduce this transport. The concentration of the amino acid in blood from foetuses remaining in the uterus was significantly increased when the dams were given 60 mg of C‐A50, indicating a reduced foetal uptake of the amino acid. It is suggested that the decreased placental transfer of the amino acid is dependent on physio‐chemical interactions (e.g. caused by hydrophobic properties) between the chlorobiphenyls and the NaK‐ATPase enzyme complex which is involv

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01048.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The effect of 3,4‐dihydroxyphenylpyruvic acid (DHPPA) on the hepatic metabolism of L‐DOPA was investigated in isolated perfused rat liver. DHPPA decreased the initial hepatic extraction and prolonged the elimination half‐life of L‐DOPA when they were added simultaneously at the ratio 1:4 (L‐DOPA: DHPPA) to the perfusate. At the ratio 1:1 DHPPA had no effect on the elimination half‐life, but decreased the initial hepatic extraction of L‐DOPA. When L‐DOPA was added alone the initial loss of L‐DOPA was 30% at 5 min. At that time the perfusion medium had passed the liver 2.5 times. Between 5 to 60 min. about 5% of the dose was extracted in a single pass through the liver. DHPPA added alone or together with L‐DOPA was rapidly converted to L‐DOPA, only about half of the DHPPA dose remained unmetabolized in the “plasma” at 2.5min.The main metabolites in bile of all the compounds tested were conjugates of homovanillinic acid and 3,4

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01049.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The metabolism of 4‐14C‐progesterone by the nasal mucosa and lung from mice and rats was investigatedin vitro.Using thin‐layer radiochromatography at least 10 and 7, yet unidentified, metabolites were found at incubation with slices from the nasal mucosa and lung, respectively. The results further indicated that the rate of progesterone metabolism was higher in the nasal mucosa than in the lung. Autoradiography of lung slices incubated with14C‐progesterone showed that a selective localization of radioactivity occurred in the bronchial

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01050.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The penetration of trimethoprim and three derivatives into bone tissue was investigated in a dog model. Our data demonstrated that the trimethoprim derivative RO 10–5970 concentrates well in bone tissue with median tissue‐to‐serum concentration ratios of 0.23 in cortical bone and 0.81 in both medulla and cancellous bone. The use of RO 10–5970 in osseous infections is appealing because oral administration is possible; therefore, clinical trials appear wa

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01051.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The relative amount of chromium excreted in rat bile after injection of Cr‐III is much less than after injection of Cr‐VI, about 0.1% and from 6–8% during 5 hours respectively, for corresponding dose levels. The liver to bile ratio was 50–100 for Cr‐III injection, for Cr‐VI the ratio was 2–3. With doses up to 18 μmol Cr/kg, only Cr‐III was found in bile even after injection of Cr‐VI. Glutathione depletion of the liver with cyclohexene oxide decreased chromium excretion in bile. Such treatment also decreased the reduction of Cr‐VI to Cr‐III in the liver cell as only Cr‐VI was found in bile. A different distribution of Cr‐III in the liver dependent on whether derived from Cr‐VI or taken up by the liver as such must be assumed. Taking into account the usual low penetration of biological membranes by Cr‐III, a possible active transport mechanism or a specific diffusable Cr

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01052.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1982.tb01053.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY