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  • 1
    Electronic Resource
    Electronic Resource
    Diazepam actions and plasma concentrations following ethanol ingestion (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 345-349 
    Details
    ISSN: 1432-1041
    Keywords: Diazepam ; ethanol ; plasma levels ; interaction ; motor performance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In eight normal volunteers, the combination of ethanol (0.5 g/kg) and diazepam (10 mg) administered orally produced a greater decrease in motor performance on a pursuit rotor than diazepam alone. The pharmacologic effect of diazepam was enhanced by 73% and this potentiation was associated with significantly greater diazepam concentrations (p〈0.01) than after diazepam alone. The failure to observe any increase in the concentrations of the principal metabolite, N-desmethyl diazepam, during the period of enhanced pharmacologic effect precludes any change in the demethylating metabolic process as being responsible. The data suggest (0.10〉p〉0.05) a trend to a smaller volume of distribution of diazepam when ethanol is administered prior to diazepam ingestion. The subjects showed acute tolerance to the effects of diazepam. Lower plasma concentrations on the ascending side of the plasma diazepam concentration versus time profile were linked with the same pharmacologic responses associated with a greater drug concentration on the descending portion, of the same curve.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00566531
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  • 2
    Electronic Resource
    Electronic Resource
    Absorption of oral and intramuscular chlordiazepoxide (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 267-274 
    Details
    ISSN: 1432-1041
    Keywords: Chlordiazepoxide ; benzodiazepines ; pharmacokinetics ; bioavailability ; intramuscular injection ; alcohol withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of oral and intramuscular (i. m.) chlordiazepoxide hydrochloride (CDX · HCl) was compared in two pharmacokinetic studies. In Study One, single 50-mg doses of CDX · HCl were administered orally and by i. m. injection to 14 healthy volunteers using a crossover design. Whole-blood concentrations of chlordiazepoxide (CDX) and its first active metabolite, desmethylchlordiazepoxide (DMCDX), were determined in multiple samples drawn after the dose. Mean pharmacokinetic variables for CDX following oral and i. m. administration, respectively, were: highest measured blood concentration, 1.65 vs 0.87 µg/ml (p〈0.001); time of highest concentration, 2.3 vs 7.6 h after dosing (p〈0.001); apparent absorption half-life, 0.71 vs 3.39 h (p〈0.001). Biphasic absorption after i. m. injection, consistent with precipitation at the injection site, was observed in 9 of 14 subjects. Based upon comparison with previous intravenous data, the completeness of absorption was 100% for oral vs 86% for i. m. CDX · HCl (p〈0.1). In Study Two, 28 male chronic alcoholics with clinical manifestations of the acute alcohol withdrawal syndrome were randomly assigned to one of four treatment conditions: 50 or 100 mg doses of CDX · HCl, by mouth or by i. m. injection. Concentrations of CDX and DMCDX, determined in plasma samples drawn every 20 min for 5 h following the dose, were significantly higher after oral administration of a given dose than at corresponding points in time after i.m. injection after the same dose. Thus absorption of oral CDX is reasonably rapid and complete, whereas the absorption rate of i. m. CDX is slow.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00716362
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  • 3
    Electronic Resource
    Electronic Resource
    Sequestration of fentanyl by the cardiopulmonary bypass (CPBP) (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 51-56 
    Details
    ISSN: 1432-1041
    Keywords: fentanyl ; cardiac surgery ; fentanyl plasma concentration ; fentanyl sequestration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Immediately following the connection of pediatric patients to cardiopulmonary bypass we have consistently observed a steep decrease in fentanyl plasma concentration (74±8.7%) (mean±SD), much greater than would have been expected from hemodilution alone (50.6%±12.0%) (p〈0.0001). Priming of the pump with 20 ng/ml of fentanyl before connection to the patients did not prevent this phenomenon. In order to study the possibility that fentanyl is sequestered by the bypass, levels of the primed drug in the bypass were assessed before connecting the pump to the children and a steep fall from 20 ng/ml to zero was shown before initiation of bypass. Pharmacokinetic assessment of fentanyl in a closed pump circuit showed that levels of 120 ng/ml fall to 2 ng/ml within 3 min and remain stable at the lower concentration for at least 30 min. Further studies have identified the membrane oxygenator as the major site of fentanyl sequestration. Concentrations across the membrane fall from 120 ng/ml to 10 ng/ml. The attached siliconized tubing is associated with a minor binding effect sufficient to reduce concentrations from 110 to 84 ng/ml. The pvc tubing, aluminium heat exchanger and plastic reservoir had no binding effect on fentanyl. The possibility that a decrease in fentanyl protein binding caused the fall in serum concentration was checked in 5 patients undergoing open heart surgery. After initiation of the cardiopulmonary bypass, there was a significant decrease in albumin serum concentrations from 32.0±2.3 mM to 15.0±1.6 mM (p〈0.0001). Since this decrease is identical to the dilutional effect anticipated on initiation of bypass, it is unlikely that there was any change in free fentanyl concentration from that observed in the prebypass period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395206
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  • 4
    Electronic Resource
    Electronic Resource
    Sequestration of fentanyl by the cardiopulmonary bypass (CPBP) (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 51-56 
    Details
    ISSN: 1432-1041
    Keywords: fentanyl ; cardiac surgery ; fentanyl plasma concentration ; fentanyl sequestration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Immediately following the connection of pediatric patients to cardiopulmonary bypass we have consistently observed a steep decrease in fentanyl plasma concentration (74±8.7%) (mean±SD), much greater than would have been expected from hemodilution alone (50.6%±12.0%) (p〈0.0001). Priming of the pump with 20 ng/ml of fentanyl before connection to the patients did not prevent this phenomenon. In order to study the possibility that fentanyl is sequestered by the bypass, levels of the primed drug in the bypass were assessed before connecting the pump to the children and a steep fall from 20 ng/ml to zero was shown before initiation of bypass. Pharmacokinetic assessment of fentanyl in a closed pump circuit showed that levels of 120 ng/ml fall to 2 ng/ml within 3 min and remain stable at the lower concentration for at least 30 min. Further studies have identified the membrane oxygenator as the major site of fentanyl sequestration. Concentrations across the membrane fall from 120 ng/ml to 10 ng/ml. The attached siliconized tubing is associated with a minor binding effect sufficient to reduce concentrations from 110 to 84 ng/ml. The pvc tubing, aluminium heat exchanger and plastic reservoir had no binding effect on fentanyl. The possibility that a decrease in fentanyl protein binding caused the fall in serum concentration was checked in 5 patients undergoing open heart surgery. After initiation of the cardiopulmonary bypass, there was a significant decrease in albumin serum concentrations from 32.0±2.3 mM to 15.0±1.6 mM (p〈0.0001). Since this decrease is identical to the dilutional effect anticipated on initiation of bypass, it is unlikely that there was any change in free fentanyl concentration from that observed in the prebypass period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553154
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of cimetidine after subchronic administration (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 741-744 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; subchronic administration ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of cimetidine on its own pharmacokinetics after subchronic administration was assessed in 8 healthy volunteers, aged 26–29 years. On control Day 1, each subject received cimetidine 300 mg i.v., and serum and urine samples were obtained. Each subject was initiated on cimetidine 600 mg b.i.d. orally for 2 weeks. There were 3 further study days repeated after 1 and 2 weeks of cimetidine dosing and 1 week after stopping cimetidine. There was no significant difference in the mean total body clearance of cimetidine among the 4 study days. Mean elimination t1/2β and Vβ were similarly unchanged. However mean renal clearance (CLR) and fe were significantly increased following 2 weeks of drug dosing (CLR 5.41 ml·min−1 kg−1; fe 0.61) compared to control (CLR 4.00 ml·min−1·kg−1; fe 0.48). Although the non renal clearance was reduced from control values of 4.29 to 3.51 ml·min−1·kg−1 following 2 weeks of dosing the difference was not significant. Dosage adjustment of cimetidine appears unnecessary after short-term dosing in the presence of normal renal function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608228
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  • 6
    Electronic Resource
    Electronic Resource
    The influence of hypothermia on the disposition of fentanyl — Human and animal studies (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 373-376 
    Details
    ISSN: 1432-1041
    Keywords: hypothermia ; fentanyl ; pharmacokinetics ; cardiopulmonary bypass ; hypothermia-induced hypoperfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of hypothermia on the disposition of fentanyl was evaluated in 18 children undergoing corrective cardiac surgery. They received a bolus of fentanyl followed by a continuous infusion which was stopped when cardiopulmonary bypass was established and profound hypothermia was achieved (18 °C–25 °C). Fentanyl plasma concentration remained essentially unchanged during hypothermia (6.45 ng/ml 5 min into hypothermia and 5.26 ng/ml 100–140 min later; p〉0.1). In subsequent experiments, the effect of hypothermia on the pharmacokinetics of fentanyl was studied in 4 piglets serving as their own controls. Both distribution volume (Vz) and total body clearance (CL) were significantly smaller during hypothermia. Our studies indicate that being a drug with a large distribution volume and a high hepatic extraction ratio, both CL and Vz are significantly reduced by hypothermia-induced hypoperfusion. In addition, TBC is influenced by the temperature-dependent hepatic metabolism of fentanyl.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543972
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    Paper (German National Licenses)
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  • 7
    Electronic Resource
    Electronic Resource
    ELECTROCARDIOGRAPHIC CHANGES DURING ETHANOL WITHDRAWAL (1976)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 273 (1976), 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.1749-6632.1976.tb52901.x
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