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  • 1
    Electronic Resource
    Electronic Resource
    Aging, cigarette smoking and oral theophylline requirement (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 33-37 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; aging ; cigarette smoking ; obstructive pulmonary disease ; plasma levels ; steady-state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a prospective study in 73 patients with obstructive pulmonary disease, aged 63.5±13.5 years (SD), it was found that theophylline dose, cigarette smoking and age were all significant determinants of the steady-state trough plasma theophylline level during oral administration of the drug. As the predictive efficiency of the three factors combined amounted only to 25%, firm dosage recommendations cannot be made. Even among elderly patients, tobacco smokers had significantly lower plasma concentrations of theophylline. It is suggested that in order to obtain trough plasma concentrations of 50 µmol/l (≈9 µg/ml), a non-smoking 50 year-old patient would require 9.8 mg/kg/day of oral theophylline, the dose increasing to 14.2 mg/kg/day in smokers of the same age. These doses should probably be reduced by 15–20% in 75 year-old patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609585
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of ethanol intake on disopyramide elimination by healthy volunteers (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 103-105 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; ethanol ; pharmacokinetics ; interaction ; metabolic clearance ; renal clearance ; diuresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of ethanol intake on disopyramide elimination was examined in an open cross-over study in six healthy volunteers. No effect of ethanol on the elimination half-life or total body clearance of disopyramide was found, although it did decrease the percentage of mono-N-dealkylated disopyramide excreted in the urine (p〈0.05) as well as the relative metabolic clearance of disopyramide (p〈0.05). The renal clearance of disopyramide was increased by 19±16% (p〈0.05) in subjects in whom ethanol caused a diuresis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544024
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  • 3
    Electronic Resource
    Electronic Resource
    Residual effect of single and repeated doses of midazolam and nitrazepam in relation to their plasma concentrations (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 595-600 
    Details
    ISSN: 1432-1041
    Keywords: midazolam ; nitrazepam ; psychomotor performance ; residual plasma drug level ; carry over effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve healthy volunteers were given either midazolam 15 mg or nitrazepam 5 mg for 7 consecutive days in a randomized cross-over trial. Self-assessment of sleep, mood or condition on awakening and adverse effects was performed, and the volunteers underwent evaluation of psychomotor performance. Hypnotic effect, judged by the classical sleep variables, showed that the drugs were more or less equal and were superior to placebo. Nitrazepam consistently produced an impaired condition on awakening and also clearly displayed a spectrum of adverse motor effects. Motor tests revealed impairment induced by both drugs, but, in the midazolam group the effect subsided during the trial period. Both drugs had a significant effect on memory, midazolam appearing to perturb certain memory functions to a greater extent than did nitrazepam. The residual plasma concentration of midazolam 11 h after treatment correlated well with the scores obtained in several of the psychomotor tests, whereas plasma nitrazepam levels were not related to performance in any subtest. When discontinued neither drugs, induced any rebound phenomenon. However, the adverse effects of nitrazepam appeared to be carried over into the adjacent placebo period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635899
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  • 4
    Electronic Resource
    Electronic Resource
    Plasma concentration of diazepam and N-desmethyldiazepam in children after a single rectal or intramuscular dose of diazepam (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 273-276 
    Details
    ISSN: 1432-1041
    Keywords: Diazepam ; N-desmethyldiazepam ; plasma levels ; rectal administration ; intramuscular administration ; children ; food intake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of diazepam and N-desmethyldiazepam after administration of diazepam solution for parenteral injection per rectum and intramuscularly was studied in 9 children (ages 3–12 years). Rectal administration of diazepam 1 mg/kg led to rapid absorption with plasma levels of 270–320 ng/ml within 5 min, and peak levels of 600–1300 ng/ml 10–60 min after administration. The absorption was comparable to that after intramuscular administration. A second peak in plasma diazepam concentration 6–12 h after dosing was observed in 6 children, which may have been due to mobilization of diazepam from the gastrointestinal mucosa produced by feeding 4 h after administration of the drug. A slowly increasing plasma level of N-desmethyldiazepam was observed during the first 24 h after administration of diazepam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00560461
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of disopyramide in patients with imminent to moderate cardiac failure (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 187-192 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; cardiac failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The parmacokinetics of disopyramide (DP) in 10 patients with imminent to moderate cardiac failure has been studied and compared with the results in normal volunteers. The biological half life of rapid distribution (T1/2 α) and of elimination (T1/2 β) were increased (11.1±4.4 min and 9.7±4.2 h, respectively). Total body clearance (Clt) was decreased (0.467±0.215 ml · min−1 · kg−1), and the volume of distribution (Vd) was slightly reduced (0.610±0.1361 · kg−1), probably due to the lower cardiac index. After oral administration, the time to peak serum concentration was increased (139±89 min), and the mean peak serum concentration (2.4±0.8% dose · 1−1) was also higher than reported in normal subjects. Comparison of the areas under the concentration versus time curves after intravenous and oral administration (AUC i. v. and AUC oral) showed that DP was almost completely absorbed, its bioavailability being 97.5±15.0%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561947
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  • 6
    Electronic Resource
    Electronic Resource
    Heating and cooling of the nitroglycerin patch application area modify the plasma level of nitroglycerin (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 625-628 
    Details
    ISSN: 1432-1041
    Keywords: Glyceryl trinitrate ; transdermal patch, pharmacokinetics, cutaneous circulation, skin temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 19 healthy volunteers wore a nitroglycerin patch releasing 10 mg per 24 h for 2 h. Subsequently, the skin area surrounding the patch was exposed to 15 min of local heating with an infrared bulb (Group A, n =10), or local cooling with an ice-pack (Group B, n = 9). The patch was protected by an insulating shield (Styrofoam). After 10 min of heating, the median (Walsh) plasma nitroglycerin level increased from 3.1 to 7.6 nmol·1−1. Body temperature remained constant. After 15 min of cooling the median plasma level had dropped from 2.1 to 1.4 nmol·1−1. The results demonstrate that changes in skin temperature may cause extensive short-term changes in the bioavailability of nitroglycerin. Presumably, a subcutaneous or cutaneous reservoir builds up during transdermal treatment, and changes in regional cutaneous blood flow affect the rate of drainage from the reservoir into the systemic circulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02284961
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  • 7
    Electronic Resource
    Electronic Resource
    Transdermal nitroglycerin: clinical and pharmacokinetic consequences of renewing the patch and the application site (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 379-381 
    Details
    ISSN: 1432-1041
    Keywords: Key words Nitroglycerin; transdermal nitrate ; pharmacokinetics ; patch renewal ; exercise test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We examined whether nitroglycerin (glyceryl trinitrate, GTN) patch treatment for 24 h could induce local cutaneous changes that impaired drug delivery and clinical efficacy. Methods: Twenty angina patients were exercise-tested after 2 and 24 h of treatment and then 2 h after patch renewal. The patch was either renewed on a new skin location or on the previous application site in a randomised, double-blind, cross-over protocol. GTN plasma concentrations and finger plethysmography were obtained before and after each exercise test. Results and conclusions: The clinical efficacy, the effect seen on plethysmography and the GTN plasma concentrations tended to increase after patch renewal, regardless of the application site of the renewed patch. Hence, cutaneous changes of clinical importance could not be demonstrated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050304
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  • 8
    Electronic Resource
    Electronic Resource
    Simultaneous determination of glyceryl trinitrate and its metabolites in plasma using capillary gas chromatography with on-column injection (1986)
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 9 (1986), S. 643-647 
    Details
    ISSN: 0935-6304
    Keywords: Capillary gas chromatography (CGC) ; Simultaneous quantitation ; Human plasma ; Glyceryl trinitrate ; Glyceryl dinitrate ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A specific, sensitive, and precise assay for simultaneous quantitation of glyceryl trinitrate (GTN) and its metabolites 1,2-and 1,3-glyceryl dinitrate (GDN) has been developed. The method involves one single extraction step with benzene, followed by evaporation at 55°C. One μl of the extract was injected onto a capillary fused silica column with trifluoropropyl as the stationary phase. The column separated all the nitrates within 17 minutes using temperature programming from 90 to 155°C. The lower limits of detection were 0.05, 0.5, and 0.1 nmol/I for GTN, 1,2-GDN and 1,3-GDN respectively. The calibration curves were linear in the concentration ranges 0.05-10.0 nmol/I (GTN), 0.5-10.0 nmol/I (1,2-GDN) and 0.1-10.0 nmol/I (1,3-GDN). Plasma concentration data from two patients receiving intravenous GTN infusion are presented.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jhrc.1240091110
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