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  • 1
    Electronic Resource
    Electronic Resource
    Rational Psycho-Pharmacology for Patients with Medical Diseases (1976)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 27 (1976), S. 407-420 
    Details
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.me.27.020176.002203
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Close correlation of acetaminophen clearance with that of conjugated benzodiazepines but not oxidized benzodiazepines (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 113-115 
    Details
    ISSN: 1432-1041
    Keywords: acetaminophen clearance ; benzodiazepines ; biotransformation ; conjugation ; drug conjugating capacity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The clearance of the antipyretic-analgesic drug acetaminophen, biotransformed in humans by glucuronide and sulfate conjugation, was evaluated in 32 healthy young and elderly volunteers. Subjects received a single 650-mg dose of acetaminophen, and multiple plasma concentrations measured over the next 12 h. Random subgroups of subjects also participated in studies of the oxidized benzodiazepines diazepam, desmethyldiazepam and alprazolam, and of the conjugated benzodiazepines lorazepam, oxazepam and temazepam. Acetaminophen clearance was not related to that of the oxidized benzodiazepines, but was highly correlated with clearance of lorazepam (r=0.70, n=11, p〈0.02), oxazepam (r=0.76, n=14, p〈0.005) and temazepam (r=0.63, n=16, p〈0.01). Thus acetaminophen may serve as a probe or marker compound to evaluate drug conjugating capacity in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544026
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  • 3
    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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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    The pharmacokinetics and pharmacodynamics of sublingual and oral alprazolam in the post-prandial state (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 439-443 
    Details
    ISSN: 1432-1041
    Keywords: Alprazolam ; benzodiazepines ; pharmacokinetics ; pharmacodynamics ; sublingual dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We gave 12 healthy male volunteers 1 mg of alprazolam or placebo on three occasions after a standard breakfast in a double-blind, randomized, single-dose, three-way crossover study. The three trials were: (a) oral alprazolam and sublingual placebo; (b) oral placebo and sublingual alprazolam; (c) placebo by both routes. Plasma alprazolam concentrations during 24 h after each dose were measured by electron-capture gas-liquid chromatography. Peak plasma concentrations were reached later after sublingual than oral dosage (2.8 vs 1.8 h, P〈0.01). Other kinetic variables were not significantly different: peak plasma concentration, 11.3 vs 12.0 ng·ml−1; elimination half-life, 12.5 vs 11.7 h; and total area under the plasma concentration versus time curve, 197 vs 186 h·ng·ml−1. Pharmacodynamic measures showed that sublingual and oral alprazolam both produced sedation, fatigue, impaired digit symbol substitution, slowing of reaction time, and impairment of the acquisition and recall of information. These changes were initially observed at 0.5 h after dosage and lasted up to 8 h. In general the two routes were significantly different from placebo but not from each other.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280132
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  • 5
    Electronic Resource
    Electronic Resource
    Actual versus reported benzodiazepine usage by medical outpatients (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 383-388 
    Details
    ISSN: 1432-1041
    Keywords: benzodiazepines ; population usage and survey ; unreported usage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Benzodiazepines are widely prescribed, and in 1979 almost 10% of the adult population was taking them. Prior studies of outpatient usage of benzodiazepines have relied on survey or prescription data, which may be confounded by noncompliance. To determine the actual use of benzodiazepines, plasma benzodiazepine concentrations were measured in 225 consecutive outpatients from a university cardiology outpatient service. Self reports indicated that the great majority of the patients (191) were taking at least one medicine, and 70 reported being on a psychotropic drug. Seventy-seven patients reported taking benzodiazepines, the majority being on bromazepam (20), diazepam (26) or oxazepam (19). In 25 of those 77 patients, the reported drug could not be detected in plasma. Conversely, in 10 of the 225 patients, benzodiazepines which were not reported were detected (diazepam or flurazepam). Of those taking benzodiazepines, many had a low concentration, suggesting intermittent rather than regular use. Thus, many patients for whom benzodiazepines are prescribed take them irregularly, and a small group uses them without reporting their prescription. These findings have implications for the clinical presentation of illness and for the possibility of drug interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543974
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  • 6
    Electronic Resource
    Electronic Resource
    Gepirone and 1-(2-pyrimidinyl)-piperazine in vitro: human cytochromes mediating transformation and cytochrome inhibitory effects (1998)
    Springer
    Psychopharmacology 140 (1998), S. 293-299 
    Details
    ISSN: 1432-2072
    Keywords: Key words Gepirone ; 1-(2-Pyrimidinyl)-piperazine ; Cytochromes P450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Biotransformation of gepirone to its principal metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), was studied in human liver microsomes and in microsomes from cDNA-transfected human lymphoblastoid cells. Formation of 1-PP from gepirone in liver microsomes proceeded with a mean apparent K m ranging from 335 to 677 μM. Coincubation with 1 μM ketoconazole reduced reaction velocity to less than 5% of control values at a gepirone concentration of 250 μM. Three other metabolites, presumed to be hydroxylated products, were also formed from gepirone. Formation of all three products was reduced to approximately 20% of control values by 1 μM ketoconazole; quinidine at 1 μM produced a small reduction in formation (91–94% of control) of two of the metabolites. 1-PP was formed from gepirone exclusively by pure P450-3A4 with a K m of 849 μM; K m values for the other metabolites were 245, 240, and 415 μM. Two of the products were also formed by P450-2D6. The results indicate that 3A4 is the principal cytochrome mediating 1-PP formation, as well as formation of the other metabolites. The properties of gepirone and 1-PP themselves as cytochrome inhibitors were tested in human liver microsomes using index reactions representing activitiy of P450-1A2, -2C9, -2C19, -2D6, -2E1 and -3A. Gepirone and 1-PP produced negligible inhibition of all these reactions. Thus gepirone at therapeutic doses in humans has a low likelihood of inhibiting P450-mediated drug metabolism involving these cytochromes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050770
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