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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography A 279 (1983), S. 615-622 
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 133-139 
    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; pharmacokinetics ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six children, aged 2 months – 4 years, received theophylline 5–6 mg/kg intravenously. Its disposition could be described by a two-compartment open model, the mean serum half life (t1/2 β) was 3.75 h, i. e., shorter than in adults, but there was a considerable interindividual variation (1.8–7.0 h, in one patient 13.3 h). Thirteen children (2 months – 4 years) received theophylline suppositories in a dose of 3.8–5.0 mg/kg, and ten (6 months – 4 years) in a dose of 8.4–14.5 mg/kg. Absorption was slow (mean half-time 43 min), incomplete and variable (biological availability 8–100%, mean 80%). Only four of the patients given the higher dose and none given the lower dose reached a therapeutic serum concentration (10–20 µg/ml). Nine children (6 months – 4 years) received rectal enemas of theophylline 4.1–9.2 mg/kg. Absorbtion was rapid (mean half-time 5.5 min) and biological availability averaged 100%. Six patients reached a serum concentration within the therapeutic range. Using the mean values of the calculated pharmacokinetic parameters, rectal enemas providing a dose of theophylline of 6–8 mg/kg t. i. d. were computed to give serum concentrations between 8–20 µg/ml, without producing too high a level during the absorption phase.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 481-494 
    ISSN: 1573-8744
    Keywords: clonidine ; pharmacokinetics ; blood and brain levels ; liver clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To investigate the pharmacokinetic behavior of clonidine, rats were given clonidine intravenously at 125, 250, and 500μg/kg and blood clonidine concentrations were followed for 6 hr. The disposition of clonidine in two brain regions was studied in rats after an i. v. dose of 500 μg/kg. The liver clearance in rats was investigated by liver perfusion techniques. The results obtained indicate that the disposition characteristics of clonidine can be described by a two-compartment open model in both rats and cats. The penetration of clonidine into tissues is rapid, and brain levels in rats were about 1.7 times higher than blood levels. Brain tissues were found to be an indistinguisible part of the central (blood) compartment. Dose-dependent pharmacokinetic behavior was found for clonidine in rats at the doses used. This was demonstrated by a decrease of both the rate constant of distribution to the peripheral compartment and the overall elimination rate constant from the body, with increase in dose. As a consequence, the volume of distribution and the clearance both decreased with increasing dose. Possible explanations for the dose-dependent behavior of clonidine are discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-8744
    Keywords: clonidine ; pharmacokinetics ; analgesia ; blood pressure effects ; smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The time course of an observed pharmacological effect is affected not only by the kinetics of the drug levels at the site of action but also by parameters such as the slope and maximum effect of the functional relationship between drug level and response. Using clonidine as a test drug, it was found that the kinetics of its effects on blood pressure and pain responses cannot be described by the time course of clonidine levels in the blood, brain, or the hypothetical tissue compartment of the two-compartment characteristics of this drug. However, the results can be explained assuming that the observed pharmacological effects of a drug are composed of the sum of responses from at least two receptor sites with different slopes and maximal effects. The effect of intravenously administered clonidine on blood pressure in the rat was found to be related to the blood concentrations at least at two receptor sites with opposite effects, one leading to a hypertensive and the other to a hypotensive response. Predictions indicate that a maximum decrease of arterial blood pressure is obtained when the steady-state blood concentration of clonidine is about 1 ng/ml and that no effect is seen at 10 ng/ml. Higher levels will produce an increase of the pressure. The kinetics of the analgesic effect of clonidine in the rat could best be related to the brain levels if the observed effect was considered to be derived from the sum of activity at two receptor sites each producing analgesia. The kinetics of the effects of clonidine on the nictitating membrane of the cat was found to be determined by the kinetics of the drug in the peripheral compartment of the two-compartment open model. Consideration of multiple receptor responses is suggested for future studies on the relationship between the kinetics of drug levels and pharmacological responses.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Chromatographia 23 (1987), S. 709-712 
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Polymer-based support ; Aldehydes ; Fluorescence detection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The aldehydes were separated by reversed phase chromatography on a polymer-based support. Acid catalysis on the column was needed to obtain sufficiently fast equilibrium between acetaldehyde and its hydrate. Deuterium labeled acetaldehyde (D3) yielded complete separation from the nonlabeled compound, probably due to a difference in hydratization. Fluorescent products were obtained by reaction between the aldehydes and a mixture of ammonia and dimedone (5.5-dimethyl-1.3-cyclohexanedione). The fluorescence was detected at 460 nm after excitation at 390 nm. A reaction time of 42 seconds at 90°C in a knitted teflon capillary produced detection limits of 0.5 and 1 ng for acetaldehyde and formeldehyde, respectively. A method for preparation of a stable reagent with low background fluorescence is described.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 30 (1995), S. 1380-1392 
    ISSN: 1076-5174
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: A general procedure for screening of amperozide, N-ethyl-4-[4,4-bis(p-fluorophenylbutyl)]-1-piperazine carboxamide, labelled with 3H and 14C was developed. Urine extracts were first fractionated by preparative reversedphase chromatography with an acetonitrile gradient elution. The collected fractions were finally analysed using a methanol gradient on packed capillary LC columns with an internal diameter of 0.32 or 0.5 mm connected to the Frit-FAB probe of a Jeol SX-102 mass spectrometer for structural analysis. A micro-gradient system dedicated for the use of deuterated solvents was constructed from two six-port switching valves to reduce the consumption of the eluents. The number of hydrogens bound to heteroatoms (OH, NH) was determined by comparing the spectra recorded from mobile phases using water and deuterium oxide. The mass spectra recorded during elution with deuterated solvents was also useful for the interpretation of the fragmentation pattern of standard compounds and unknown metabolites. The technique proved especially useful to differentiate between hydroxylation and N-oxidation which gave the same increase in molecular mass by 16 u but a difference in the number of exchangeable protons. Metabolites formed by oxidative N-dealkylation of amperozide either at the basic nitrogen or at the N-ethylcarboxamide nitrogen were identified. Additional metabolites derived from deethylated amperozide inovlving N-oxidation of the basic nitrogen of the piperazine ring and/or hydroxylation of the piperazine ring were identified. Metabolites formed by oxidative N-dealkylation and opening of the piperazine ring were also identified.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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