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  • 1
    Electronic Resource
    Electronic Resource
    Studies of the bioavailability of nitroglycerin from a transdermal therapeutic system (Nitroderm TTS) (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 7-12 
    Details
    ISSN: 1432-1041
    Keywords: nitroglycerin ; plasma concentration ; transdermal administration ; bioavailability ; pharmacodynamics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 healthy volunteers, intravenous infusions of nitroglycerin 4.8 and 10.6 µg/min yielded mean steady-state plasma concentrations of 0.5±0.02 and 0.82±0.04 ng/ml as determined by a gas chromatographic/mass spectrometric method. The plasma concentrations reached in the same subjects 17 h after application of Nitroderm TTS 5 and 10 with in vivo release rates of 3.7 and 5.7 µg/min were 0.28±0.01 and 0.37±0.01 ng/ml, respectively. Thus, 75% of the quantity of nitroglycerin released by the systems passed into the circulation. The inter-individual and intra-individual variations in plasma concentrations were similar for both modes of administration. The nitroglycerin-induced morphological changes in the fingerpulse wave were clearly dose-dependent, but it seems that this pharmacodynamic parameter is determined less by the plasma concentration than by the nitroglycerin content of the vascular wall.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395198
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  • 2
    Electronic Resource
    Electronic Resource
    Comparative pharmacokinetic profiles of metoprolol and chlorthalidone administered alone or in combination to healthy volunteers (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 655-660 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; chlorthalidone ; co-administration ; pharmacokinetics ; healthy subjects ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A potential pharmacokinetic interaction between the beta-blocking drug, metoprolol, and the diuretic, chlorthalidone, has been investigated in three single or multiple dose studies in healthy volunteers. The pharmacokinetic profile of metoprolol 100 mg was not affected by pretreatment with or co-administration of chlorthalidone 25 mg twice daily. Similarly, the pre-dosing steady-state level of chlorthalidone during chronic treatment and its blood level profile after a single 25 mg dose were not affected by metoprolol. The bioavailabilities of the 2 drugs administered in combination were identical to those observed when each drug was administered alone. These studies demonstrate that there is no pharmacokinetic interaction between metoprolol and chlorthalidone when doses of 100 and 25 mg, respectively, are co-administered twice daily.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542217
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  • 3
    Electronic Resource
    Electronic Resource
    Diffusion of oxyphenbutazone into synovial fluid, synovial tissue, joint cartilage and cerebrospinal fluid (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 107-112 
    Details
    ISSN: 1432-1041
    Keywords: oxyphenbutazone ; inflammation ; diffusion ; synovial fluid ; synovial tissue ; cerebrospinal fluid ; joint cartilage ; tissue level ; CSF level ; joint level ; distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The diffusion of oxyphenbutazone into synovial and cerebrospinal fluids and synovium and joint cartilage was investigated in 25 patients receiving short-term treatment. In the synovial fluid, the mean oxyphenbutazone concentration, was 57.1±13.4% of the plasma level, due to its excellent diffusion into the joint cavity. In synovial tissue, the oxyphenbutazone level was higher in patients with severe inflammation than in those with no or little inflammation. Penetration into joint cartilage is less than into synovial tissue. In cerebrospinal fluid the concentration was close to the level of free plasma oxyphenbutazone. The findings show increased diffusion of oxyphenbutazone towards its site of action in inflammation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544025
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  • 4
    Electronic Resource
    Electronic Resource
    Studies of the bioavailability of nitroglycerin from a transdermal therapeutic system (Nitroderm TTS) (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 7-12 
    Details
    ISSN: 1432-1041
    Keywords: nitroglycerin ; plasma concentration ; transdermal administration ; bioavailability ; pharmacodynamics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 healthy volunteers, intravenous infusions of nitroglycerin 4.8 and 10.6 µg/min yielded mean steady-state plasma concentrations of 0.5±0.02 and 0.82±0.04 ng/ml as determined by a gas chromatographic/mass spectrometric method. The plasma concentrations reached in the same subjects 17 h after application of Nitroderm TTS 5 and 10 with in vivo release rates of 3.7 and 5.7 µg/min were 0.28±0.01 and 0.37±0.01 ng/ml, respectively. Thus, 75% of the quantity of nitroglycerin released by the systems passed into the circulation. The inter-individual and intra-individual variations in plasma concentrations were similar for both modes of administration. The nitroglycerin-induced morphological changes in the fingerpulse wave were clearly dose-dependent, but it seems that this pharmacodynamic parameter is determined less by the plasma concentration than by the nitroglycerin content of the vascular wall.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553146
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Human pharmacological studies of a new transdermal system containing nitroglycerin (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 473-480 
    Details
    ISSN: 1432-1041
    Keywords: nitroglycerin ; transdermal system ; transdermal absorption ; plasma concentration ; haemodynamic effects ; tolerability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A new transdermal therapeutic system (TTS) for the administration of nitroglycerin (NTG) was tested in human pharmacological studies in 26 healthy volunteers. Plasma concentrations and haemodynamic responses were determined after the application of the system in different dosages. The concentrations of NTG reached in the plasma were uniform and dose-related, i.e. dependent on the drug-release area, and showed only minor inter-individual variation. They remained almost constant as long as the system was in contact with the skin. Renewal of the system caused no appreciable change in the plasma concentration. The haemodynamic effects, like those of all nitrates, were not clearly related to the dose administered, and were not always dependent on the plasma concentration. Upon repeated application, NTG-TTS was well tolerated locally and systemically and led to no alteration in blood chemistry or haematological parameters. The typical nitrate headaches disappeared after a few days. The presence of the system on the skin caused no discomfort or inconvenience.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609617
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  • 6
    Electronic Resource
    Electronic Resource
    Plasma concentrations and haemodynamic effects of nitroglycerin during and after intravenous infusion in healthy volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 99-106 
    Details
    ISSN: 1432-1041
    Keywords: nitroglycerin ; i.v. infusion ; plasma level ; haemodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of nitroglycerin, infused intravenously at 3.4 and 7.5 µg/min over 30 min, on haemodynamic parameters were determined in the morning and the afternoon in a randomized, placebo-controlled study in 5 healthy volunteers. The mean steady-state concentrations of nitroglycerin reached in the plasma during the infusions of 3.4 and 7.5 µg/min were 0.35±0.06 ng/ml and 0.64±0.22 ng/ml, respectively. Wide inter-individual variation was noted. The nitroglycerin-induced increase in the orthostatic rise in heart rate and the change in digital-pulse-wave morphology roughly paralleled the plasma concentration, whereas the reduction in systolic blood pressure in the upright position was still evident 15 mins after the infusion, i.e. when nitroglycerin was no longer measurable in plasma. No significant diurnal variation in vascular sensitivity to the vasodilative action of nitroglycerin was demonstrable. The change in pulse-wave morphology resulting from the reduction in peripheral resistance (shift of the dicrotic wave in the descending limb towards the base-line) proved to be the most sensitive haemodynamic parameter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545962
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  • 7
    Electronic Resource
    Electronic Resource
    Absorption kinetics and model characteristics of orally administered pirprofen (1983)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 425-433 
    Details
    ISSN: 1573-8744
    Keywords: pirprofen ; two-compartment model ; oral absorption ; influence of formulation, dose, food ; parameter estimates ; prediction of kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pirprofen kinetics can be described by a linear two-compartment model. Absorption kinetics and model parameters were determined by the incremental method from 48 pirprofen plasma concentration-time profiles obtained after administration of single oral pirprofen doses. Statistical comparison of the results gave information on the influence of formulation, dose, and food on pirprofen absorption. The rate of absorption decreased significantly when pirprofen was administered as a capsule in comparison with a solution. The dose (200 mg compared with 100 mg) had no marked influence on the absorption rate. Food delayed absorption. Pirprofen model parameters, estimated as the median values of the results obtained from the 48 sets of data, permitted the plasma kinetics of the drug after single and repeated doses to be predicted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01058959
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  • 8
    Electronic Resource
    Electronic Resource
    An incremental method for the study of the absorption of drugs whose kinetics are described by a two-compartment model: Estimation of the microscopic rate constants (1983)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 401-424 
    Details
    ISSN: 1573-8744
    Keywords: absorption kinetics ; one- and two-compartment models ; iterative process ; estimation of model parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A method is proposed for estimating the overall absorption kinetics of drugs (expressed as percent of total amount absorbed versus time) from plasma data. It is applicable to the study of drugs whose kinetics can be described by linear one- or two- compartment models. Use is made of an iterative process based on the differential equations of the model and on linear interpolation of plasma data. The method does not require that the overall absorption kinetics should be apparent first-order and/or that the model parameters should be estimated from a previous experiment. It was tested for the influence of data scatter: added noise (CV= 10%) resulted in a variability of percent absorbed versus time of the same order of magnitude. During the calculations, the microscopic rate constants are estimated and optimalized. Data scatter resulted in wide variations in the estimates of the two-compartment model parameters. However, when a sufficiently large number of plasma concentration-time curves were studied, an average model could be determined with a reasonable precision. Model kinetics calculated from the related parameter estimates were in agreement with the theory. The method permits the exploitation of the various plasma concentration-time curves which are available after the development of an orally administered drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01058958
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  • 9
    Electronic Resource
    Electronic Resource
    Gas chromatographic mass spectrometric determination of 1,2,3-propanetrioltrinitrate (nitroglycerin) in human plasma using the nitrogen-15 labelled compound as internal standard (1982)
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 9 (1982), S. 333-335 
    Details
    ISSN: 0306-042X
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A method for the quantitative determination of 1,2,3-propanetrioltrinitrate (nitroglycerin) in human plasma by gas chromatography mass spectrometry has been developed. After addition of 1,2,3-propanetriol(15N)trinitrate as internal standard, plasma (1 ml) is extracted by a mixture of pentane and methyl acetate (90:10). The extracts are purified by partition between, first, the extraction solvent and a mixture of acetonitrile and water (60:40) and, secondly, the resultant aqueous phase and benzene. The solvent is evaporated to a small volume before injection. The fragment ions at m/z 46 and 47 are monitored for the measurement of the [NO2]+ and [15NO2]+ ions using electron impact ionization. The mean recovery (%) ±SD in blind plasma samples spiked with amounts in the concentration range 0.35-3.52 nmol I-1, was 97.4 ± 9.0 (n = 58). Within a day, recovery experiments gave rise to coefficients of variation of 9.6, 6.4 and 2.7% at the levels 0.44,0.88 and 11 nmol I-1, respectively. Concentrations in plasma down to about 0.2 nmol I-1 (50 pg mI-1) could be estimated. Percent recovery of duplicate determinations in the range 0.5-1.96 nmol I-1± SD was 99.4 ± 6.0 (n = 80).
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bms.1200090805
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  • 10
    Electronic Resource
    Electronic Resource
    Quantitative determination of nitroglycerol in human plasma by gas chromatography negative ion mass spectrometry using 15N labelled nitroglycerol as internal standard (1984)
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 11 (1984), S. 276-277 
    Details
    ISSN: 0306-042X
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Negative ionization resulted in the simplification of a previously published method. The new method permits the determination of 0.25 nmol l-1 nitroglycerol in plasma with a coefficient of variation of 9.1%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bms.1200110605
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