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  • 1
    Electronic Resource
    Electronic Resource
    CSF penetration and pharmacokinetics of midazolam (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 247-251 
    Details
    ISSN: 1432-1041
    Keywords: midazolam ; CSF penetration ; pharmacokinetics ; benzodiazepines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The passage of midazolam, a new benzodiazepine derivative with highly water-soluble salts, into cerebrospinal fluid (CSF) was studied after a single oral dose of 15 mg (n=23), a single i.m. injection of 0.075 or 0.150 mg/kg (n=8), or a single i.v. dose of 0.075 mg/kg (n=26). Contrary to previous studies of diazepam and flunitrazepam, the rapid clinical effect of midazolam cannot be explained by rapid passage into human lumbar CSF. In only four cases following intravenous injection was there a measurable amount of drug in lumbar CSF (lower limit of assay sensitivity=2 ng/ml). After both oral (n=10) and intramuscular (n=8) administration, midazolam was rapidly absorbed, with attainment of the peak serum level after about 0.5 h. The pharmacokinetic parameters following i.v. injection of midazolam (n=6) explain its rapid but brief duration of action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543799
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  • 2
    Electronic Resource
    Electronic Resource
    Comparison of radioreceptor assay and radioimmunoassay for atropine: Pharmacokinetic application (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 613-617 
    Details
    ISSN: 1432-1041
    Keywords: atropine ; radioreceptor assay ; radioimmunoassay ; serum levels ; pharmacokinetics ; assay comparison
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A membrane suspension prepared from rat brain was able to bind the potent muscarinic antagonist quinuclidinyl benzilate (QNB). The KD for binding was 0.48 nM and Bmax was 1.42 pmol/mg protein. Atropine competitively inhibited the binding of tritiated QNB to muscarinic receptors. This new radioreceptor assay (RRA) for atropine has been compared with a radioimmunoassay (RIA) for atropine. The RRA measures only the active component of atropine, 1-hyscyamine and in this respect it differs from the RIA. As little atropine as 1.25 ng/ml (4.33 nmol/l) in a 25 µl serum sample could be reliably assayed by the RRA. Using both assay techniques the pharmacokinetics of atropine was studied after a single 0.02 mg/kg i.v. dose given to 8 anaesthetized patients. The half-life calculated by the RRA was 3.7±2.3 h (m ± SD) and by the RIA 4.3±1.7 h. Both the volume of distribution and the total clearance were higher according to the RRA than the RIA: 3.9±1.5 vs 1.7±0.71/kg and 15.4±10.3 vs 5.9±3.6 ml/min/kg, respectively. The AUC measured by the RRA and RIA was 29.8±18.9 and 103.9±110.7 µg·h/l, respectively. The differences in the pharmacokinetics according to the 2 methods are presumably due to preferential tissue uptake of the l-form.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543495
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Transfer of free and conjugated oxazepam across the human placenta (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 301-304 
    Details
    ISSN: 1432-1041
    Keywords: oxazepam ; oxazepam glucuronide ; placental transfer ; fetal drug level ; pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six women, 13 to 16 weeks pregnant, and 12 women at 38 to 40 weeks gestation, received oral oxazepam about 12 h before legal abortion, by hysterotomy in the former and before elective caesarean section in the latter group. The concentrations of free and conjugated oxazepam in maternal and fetal plasma were determined by gas-liquid chromatography. In early pregnancy the mean ratio between the plasma concentration of total (free + conjugated) drug in the umbilical cord and a maternal vein was 0.6, whereas in late pregnancy the ratio vein was 1.1. Both in early and late pregnancy, the free and glucuronide conjugate of oxazepam were found in the fetus at concentrations which indicated transplacental passage of the parent drug and its metabolite. There was great interindividual variation in the plasma levels both of free and conjugated oxazepam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00625804
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  • 4
    Electronic Resource
    Electronic Resource
    Penetration of lidocaine and its active desethylated metabolite into cerebrospinal fluid in man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 639-641 
    Details
    ISSN: 1432-1041
    Keywords: Lidocaine ; CSF penetration ; monoethylglycinxylidide ; glycinxylidide ; pharmacokinetics ; serum protein binding ; membrane permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Penetration into lumbar cerebrospinal fluid (CSF) of lidocaine and its active desethylated metabolite, monoethylglycinxylidide (MEGX), has been studied in 10 neurological patients after a single subcutaneous injection of 2 mg/kg prior to lumbar puncture. An HPLC method was used to assay lidocaine, MEGX and glycinxylidide (GX) in serum and CSF. The serum protein unbound fraction of lidocaine was determined by equilibrium dialysis. The mean peak serum lidocaine concentration was found 25 minutes after injection, and the corresponding peak CSF level occurred after 70 min. A similar slow penetration of MEGX into CSF was observed, which indicates low membrane permeability for these two agents. No GX was found. The steadily increasing CSF lidocaine/serum total lidocaine ratio throughout the period of study up to 120 min and the higher level in CSF than the corresponding unbound fraction of the total serum lidocaine indicate that serum protein binding is not the sole determinant of the penetration of lidocaine into lumbar CSF. Rapid accumulation in brain tissue and diffusion back into cerebral extracellular fluid and to lumbar CSF may also occur. The apparent slow membrane penetration of lidocaine and its desethylated metabolite may be one reason for the difficulty of controlling lidocaine infusion rates according to therapeutic effectiveness and side-effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542352
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Midazolam versus atropine plus pethidine as premedication in children (1984)
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 39 (1984), S. 0 
    Details
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effects of oral midazolam or intramuscular atropine and pethidine used as premedication in two groups of 35 children over 5 years of age were studied. There was some evidence that the anxiolytic effect of midazolam was rather better than that of atropine plus pethidine, but, in other respects, subjective assessments in the two patient groups were similar. Intramuscular atropine caused tachycardia and subjective side-effects, nevertheless children appear to require anticholinergics during premedication because of excessive salivary secretion, especially during extubation. Oral midazolam is a new anxiolytic drug which can be used as an alternative to existing premedicant drugs, but, in children, it should still be combined with an anticholinergic agent. No correlation between serum levels of midazolam or atropine and their clinical effects was found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2044.1984.tb07231.x
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  • 6
    Electronic Resource
    Electronic Resource
    Comparison of midazolam and flunitrazepam for night sedation (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 37 (1982), S. 0 
    Details
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In a double-blind randomised study midazolam 15 mg and flunitrazepam 2 mg caused a significantly better night's sleep than placebo. Midazolam had a moderate sedative effect the following morning but, in other respects studied, no residual effects were found. In contrast, flunitrazepam decreased both the degree of apprehension and excitement the following morning. Flunitrazepam also inhibited salivary secretion and caused less cardiovascular changes than placebo or midazolam. The dose of thiopentone needed for induction of anaesthesia was significantly lower in those given flunitrazepam. The results show that midazolam is a potent sedative agent with a short duration of action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2044.1982.tb01854.x
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