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  • Analytical Chemistry and Spectroscopy  (3)
  • chronic administration  (1)
  • 1
    Electronic Resource
    Electronic Resource
    A “once a day administration” sustained-release theophylline formulation: Disposition and pharmacokinetics (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 325-328 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; sustained release ; pharmacokinetics ; chronic administration ; healthy volunteers ; plasma levels ; GCMS assay ; stable isotope technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new sustained-release preparation of theophylline (Dilatrane à Action Prolongée capsules filled with homogenous microgranules) has been after its studied administration to 7 healthy volunteers at 8 p.m. in order to achieve therapeutic levels at night and in the morning. In separate trials the test dose of 500 or 600 mg was administered for 7 days, once daily at 8 p.m. Plasma theophylline levels were measured by capillary gas chromatography with a mass specific detector after pentylation, using internal standards labelled with stable isotopes (15N-1,3 and 13C-2 theophylline). The new sustained-release preparation showed a monophasic regular absorption phase with very low interindividual variability. After administration, the plasma level stayed within 80% of the peak levels for 8.5±1.5 h. There was a good correlation between the dose and the steady state plasma level (r=0.9587; p〈0.05). This preparation can be chronically administered once daily day at 8 p.m. in order to achieve a therapeutic level during the night and the morning, and to provide sufficient protection during the nycterohemeral period, with a once dose a day schedule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542169
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  • 2
    Electronic Resource
    Electronic Resource
    Study of deuterium isotope effects on protein binding by gas chromatography/mass spectrometry. Caffeine and deuterated isotopomers (1987)
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 14 (1987), S. 653-657 
    Details
    ISSN: 0887-6134
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A study of the binding to human serum albumin (HSA) of caffeine and its deuterated isotopomers, 1-C2H3-, 3-C2H3-, 1,7-(C2H3)2-, 3,7-(C2H3)2- and 1,3,7-(C2H3)3-caffeine, was performed by equilibrium dialysis. Free and bound fractions were measured by gas chromatography/mass spectrometry. Important and significant (Fischer and Student tests) isotope effects were observed on binding parameters: sites total concentration (N = 1732) μM for 1,3,7-(C2H3)3-caffeine versus 822 μM for caffeine; number of sites (n = 3 for 1,3,7-(C2H3)3-caffeine v. 1 for caffeine); and extent of binding (46% for 1,3,7-(C2H3)3-caffeine v. 27% for caffeine).A study of competition for HSA binding between caffeine and its 1,3,7-(C2H3)3- and 3,7-(C2H3)2-isotopomers confirmed the results obtained in direct binding studies. These isotope effects are discussed in terms of (a) tools for molecular pharmacology, (b) precautions to be taken when such labelled drugs are used in clinical pharmacology.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bms.1200141115
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  • 3
    Electronic Resource
    Electronic Resource
    Study of isotope effects on protein binding by gas chromatography/mass spectrometry of theophylline-phenobarbitone and 2H, 13C, 15N isotopomers (1988)
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 17 (1988), S. 245-250 
    Details
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We describe a comparative study of human serum albumin (HSA) binding by equilibrium dialysis (pH 7.4, 37°C, 3 h) for two groups of isotopic analogues: theophylline and 1-C(2H3)theophylline; unlabelled, 5(ethyl(2H5)),-5(phenyl(2H5)) and 1,3-15N;2-13C-phenobarbitone. Bound and free drug fractions are quantified by combined gas chromatography/mass spectrometry. In three instances, protein binding parameters are greatly affected by isotopic substitution, namely for: theophylline and 1-C(2H3)theophylline with isotope effects on total binding site concentration (N), affinity constant (Ka) and extent of HSA binding (%) respectively, equal to: NL/NH=0.51; KaL/KaH = 1.78; %L/%H = 0.96 (L (light) and H (heavy) represent the unlabelled and labelled analogue respectively); phenobarbitone/-5-(phenyl(2H5))phenobarbitone, NL/NH = 1.72; KaL/KaH = 0/56; %L/%H = 1.26; phenobarbitone/1,3-15N;2-13C phenobarbitone, NL/NH = 2.95; KaL/KaH = 0.44; %L/%H = 1.32, together with a change from one (saturable) to two (saturable + non-saturable) families of albumin binding sites in the latter case. Contrasting with these data, no HSA binding isotope effect was observed on phenobarbitone C5 ethyl deuteration.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bms.1200170403
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  • 4
    Electronic Resource
    Electronic Resource
    Study of theophylline metabolism in premature human newborns using stable isotope labellingAbbreviation: DMX = dimethylxanthine. (1980)
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 7 (1980), S. 189-192 
    Details
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new metabolic pathway of theophylline has been investigated in premature human newborns using the ion cluster technique of stable isotope labelling combined with gas chromatography mass spectrometry. Labelled caffeine, paraxanthine and theobromine have been found in plasma and urine of two preterm newborns receiving [1,3-15N], [2-13C] theophylline for the treatment of primitive apneas. Theophylline is converted to caffeine by N-7 methylation. In adults, the inverse process exists wherein caffeine is demethylated to give theophylline.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bms.1200070503
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