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  • 1
    Electronic Resource
    Electronic Resource
    Studies with Corticotropin. III. Determination of the Structure of β-Corticotropin1 and its Active Degradation Products (1956)
    s.l. : American Chemical Society
    Journal of the American Chemical Society 78 (1956), S. 5067-5076 
    Details
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ja01600a067
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  • 2
    Electronic Resource
    Electronic Resource
    The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 311-315 
    Details
    ISSN: 1432-1041
    Keywords: Key wordsTerfenadine ; Grapefruit juice ; QT interval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To determine whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by the concomitant administration of grapefruit juice. Methods: Six healthy volunteers were recruited for a balanced cross-over study. Each volunteer received 120 mg terfenadine 30 min after drinking 300 ml of either water or freshly squeezed grapefruit juice. The alternative treatment was administered on the second study day 2 weeks later. Measurements of the area under the terfenadine plasma concentration-time curve (AUC), maximum terfenadine concentration (Cmax) and the time to maximum concentration (tmax) were made, and the corrected QT (QTc) interval was measured from the surface electrocardiogram. Results: Terfenadine was quantifiable in plasma in all 6 subjects on both study days for up to 24 h post-dosing. The AUC of terfenadine was significantly increased by concomitant grapefruit administration (median values 40.6 vs 16.3 ng · ml−1 · h), as was the Cmax (median values 7.2 vs 2.1 ng · ml−1). The tmax was not significantly increased and there was no significant change in the median QTc interval despite the increased terfenadine levels. The 95% confidence interval for the difference in the change in QTc interval at Cmax was −13 to +38 ms. Conclusion: Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in terfenadine bioavailability, but the increase observed in this study did not lead to significant cardiotoxicity in normal subjects. However, this does not exclude the risk of cardiotoxicity in high-risk subjects given greater doses of grapefruit juice over longer periods of time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050296
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  • 3
    Electronic Resource
    Electronic Resource
    Disposition and oxidative metabolism of phenylbutazone in man (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 359-366 
    Details
    ISSN: 1432-1041
    Keywords: Phenylbutazone ; 14C-label ; oxyphenbutazone ; gas chromatography ; disposition ; oxidative metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption and elimination of orally administered14C-phenylbutazone and the role of oxidation in its metabolism have been studied. The main routes of excretion of14C-phenylbutazone and its metabolites were investigated in 3 patients with rheumatoid arthritis, and in 1 patient with a T-tube in the common bile duct. Up to 9 days after an oral dose of14C-phenylbutazone 600 mg (30 µCi) 63% of the radioactivity was found in the urine and 14% had appeared in the faeces. The cumulative excretion of radioactivity in bile amounted to 9.5% of the dose in 4 days. Only 1% of the radioactivity in the urine and bile was due to unchanged phenylbutazone. The role of oxidative metabolism of phenylbutazone in healthy human subjects was studied by gas chromatography. In 3 subjects given a single dose of phenylbutazone 600 mg, only 8.3% of the dose was excreted in urine as oxidized metabolites after 5 days. However, in 5 patients who had taken phenylbutazone for more than 5 weeks, these metabolites accounted for 23.4% of the dose. These results suggest that oxidative metabolism becomes more important after continued administration of the drug. After a single dose of phenylbutazone, the side-chain oxidized metabolite (II) was the major free derivative excreted in urine, but the ring oxidized metabolite, oxyphenbutazone (I), was much more important than the former in plasma. However, after prolonged treatment there was little difference between the concentration of the two metabolites in plasma. This finding suggests that side-chain oxidation is increased relative to ring oxidation on prolonged treatment with phenylbutazone. A third derivative containing hydroxyl groups both in the phenyl ring and in the side-chain (metabolite III) was found in urine in experiments with phenylbutazone, but in only one out of 3 volunteers given repeated doses of oxyphenbutazone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00566533
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and concentration-effect relationships of clonidine in essential hypertension (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 463-469 
    Details
    ISSN: 1432-1041
    Keywords: Essential hypertension ; clonidine ; plasma levels ; concentration-effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of oral doses of 300 µg of clonidine hydrochloride on blood pressure, sedation and saliva production in 5 essential hypertensives were qualitatively similar to the effects in normotensive subjects. Peak plasma clonidine concentration (1.34±0.28 ng/ml) and plasma half-life (10.0 ±0.8 h) were similar to normotensives. During chronic oral dosing there was no evidence of drug accumulation. Some tolerance to the sedative and salivary flow effects occurred but no tolerance to the hypotensive effect was observed. There was a linear relationship between reduction in saliva flow and plasma levels of clonidine. The hypotensive effect was also related to plasma level at low concentrations. At plasma levels 〉1.5 ng/ml the hypotensive effect was diminished. This loss of effect at high plasma concentration may be related to the peripheral, post-synaptic alpha-adrenoceptor agonist action of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561067
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  • 5
    Electronic Resource
    Electronic Resource
    Influence of liver disease and environmental factors on hepatic monooxygenase activity in vitro (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 39-46 
    Details
    ISSN: 1432-1041
    Keywords: liver disease ; environmental factors ; cytochrome P-450 ; NADPH-cytochrome c reductase ; aryl hydrocarbon hydroxylase ; caffeine ; alcohol ; cigarette smoking ; meat consumption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of liver disease and environmental factors on hepatic microsomal cytochrome P-450 content, NADPH-cytochrome c reductase (reductase) activity and aryl hydrocarbon hydroxylase (AHH) activity have been simultaneously investigated in 70 patients undergoing diagnostic liver biopsy. The activity of reductase was not significantly affected by the presence of liver disease or any of the environmental factors studied. Cytochrome P-450 content decreased with increasing severity of liver disease whereas AHH activity was only significantly reduced in biopsies showing hepatocellular destruction. None of the parameters of monooxygenase activity varied significantly with the age or sex of the patients. Alcohol excess was associated with decreased cytochrome P-450 content and AHH activity and this effect was independent of the histological status of the biopsy. Both high caffeine intake and cigarette smoking increased AHH activity in the absence of any change in cytochrome P-450 content. There was a positive correlation between the number of meat meals eaten per week and cytochrome P-450 content. Chronic treatment with enzyme-inducing anticonvulsants appeared to increase both cytochrome P-450 content and AHH activity. Despite differential effects of liver disease and environmental influences on cytochrome P-450 content and AHH activity there was a highly significant correlation between the two parameters. The results of the present study correlate well with the known effects of disease and environment on drug metabolism in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00554665
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  • 6
    Electronic Resource
    Electronic Resource
    Differential induction of antipyrine metabolism by rifampicin (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 155-160 
    Details
    ISSN: 1432-1041
    Keywords: rifampicin ; antipyrine ; 3-hydroxymethylantipyrine ; 4-hydroxyantipyrine ; norphenazone ; cytochrome P-450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Antipyrine is oxidised to three main metabolites in man. There is evidence that the different metabolites are products of different forms of cytochrome P-450. The effect of rifampicin administration for two weeks on the rates of formation of these metabolites was investigated in healthy volunteers. Rifampicin increased antipyrine clearance and shortened its half-life. Two weeks after stopping rifampicin the induction had largely been reversed. Clearance to all three metabolites was increased by rifampicin. Clearance to 3-hydroxymethylantipyrine was increased from 7.8±0.9 ml/min to 13.3±1.3 ml/min, to norphenazone from 5.8±0.6 ml/min to 19.3±2.1 ml/min and to 4-hydroxyantipyrine from 14.3±2.2 ml/min to 21.9±3.9 ml/min. Thus clearance to norphenazone was increased to a much greater extent than to either of the other two metabolites. It is concluded that this provides evidence for the involvement of at least two different forms of cytochrome P-450 in antipyrine metabolism in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637517
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  • 7
    Electronic Resource
    Electronic Resource
    DIFFERENCES IN THE METABOLISM OF DRUGS DEPENDING UPON THEIR ROUTES OF ADMINISTRATION (1971)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 179 (1971), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1971.tb46893.x
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  • 8
    Electronic Resource
    Electronic Resource
    Planning for Changed Expectations (1973)
    [s.l.] : Nature Publishing Group
    Nature 242 (1973), S. 381-382 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] THERE are now 350,000 qualified scientists and engineers (QSEs) in Britain, alongside a population of 550,000 who have reached a similar level of further education outside science. At present, the annual output of 15,000 scientists and 10,000 engineers is showing no sign of increase, and we seem to ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/242381a0
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  • 9
    Electronic Resource
    Electronic Resource
    Bis(trifluoromethyl)aryl derivatives for drug analysis by gas chromatography electron capture negative ion chemical ionization mass spectrometry. Application to the measurement of low levels of clondine in plasma (1984)
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 11 (1984), S. 435-440 
    Details
    ISSN: 0306-042X
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A gas chromatographic mass spectrometric assay for clonidine in plasma with a detection limit of a few picograms per ml was required. The p-trifluoromethylbenzyl, pentafluorobenzyl and pentafluorobenzoyl derivatives of clonidine were synthesized and the electron capture negative ion chemical ionization mass spectra of these compounds show extensive fragmentation with prominent ions at m/z 35 and 37 due to the two chlorine atoms in the clonidine molecule. Selected ion monitoring of specific high mass ions in these mass spectra indicated that the required sensitivity could not be obtained with these derivatives. Several bis(trifluoromethyl)pyrimidines were synthesized and these compounds were found to give an intense negative ion current under conditions of resonance electron capture. Consequently, a derivative of clonidine containing a bis(trifluoromethyl)aryl group was synthesized by reacting the drug with 3,5-bis(trifluoromethyl)benzoyl chloride. The negative ion mass spectrum of the reaction product has a base peak at m/z 673 and, when this ion is specifically monitored, an amount of derivative equivalent to 1 picogram of clonidine can be detected. This allowed the development of an assay for clonidine in plasma with a precision of 8% (SD) at 50 pg ml-1, 22% (SD) at 20 pg ml-1 and a lower limit for quantitative determination of 10 pg ml-1. Plasma concentrations of clonidine In 10 subjects given a single 50μg oral dose are reported.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bms.1200110813
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  • 10
    Electronic Resource
    Electronic Resource
    An assay for 2-amino-3,8-dimethylimidazo[4,5-ƒ]-quinoxaline and 2-amino-3,4,8-trimethylimidazo-[4,5-ƒ]quinoxaline in fried beef using capillary column gas chromatography electron capture negative Ion chemical ionization mass spectrometry (1988)
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 16 (1988), S. 221-224 
    Details
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A gas chromatographic/mass spectormetric assay has been developed for the simultaneous measurement of 2-amino-3,8-dimethylimidazo[4,5-ƒ]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-ƒ]quinoxaline (DiMeIQx) in fried beef. The method employs capillary column gas chromatography, electron capture negative ion chemical ionization mass spectrometry and a stable isotope labelled analogue of MeIQx as common internal standard. Two patties of lean minced beef which had been cooked separately were analysed and found to contain both compounds (patty 1:2.4 ng MeIQx g-1 meat, 1.2 ng DiMeIQx g-1 meat; patty 2: 1.3 ng MeIQx g-1 meat, 0.5 ng DiMeIQx g-1 meat). Neither compound was present in the meat prior to cooking.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bms.1200160140
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