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  • 1
    Electronic Resource
    Electronic Resource
    The sulfoxidation of fluphenazine in schizophrenic patients maintained on fluphenazine decanoate (1987)
    Springer
    Psychopharmacology 93 (1987), S. 369-373 
    Details
    ISSN: 1432-2072
    Keywords: Schizophrenia ; Fluphenazine decanoate ; Metabolic sulfoxidation ; Fluphenazine sulfoxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Highly sensitive radioimmunoassays were applied to study the sulfoxidation of fluphenazine in 30 schizophrenic patients maintained on either 5 mg or 25 mg fluphenazine decanoate by intramuscular injection every 14 days over a period of 6 months. The presence of the sulfoxide metabolite was detected in all but one of the patients, such that 97% of the 340 plasma samples analysed contained the metabolite. Interpatient variations in plasma levels of fluphenazine, fluphenazine sulfoxide, and in drug to metabolite plasma level ratios were several fold higher than the corresponding intrapatient variations at both dosages. There were statistically significant tendencies for mean plasma fluphenazine levels to rise and mean plasma sulfoxide levels to fall over the 6-month period of study among patients on the high dose, consistent with our previously reported observation that it takes 3–6 months to establish a steady state of fluphenazine with this dosage regimen. By contrast, there were no statistically significant changes in mean plasma levels of either fluphenazine or its sulfoxide in patients on the low dose. Nevertheless, there was a significant rise in fluphenazine to fluphenazine sulfoxide mean plasma level ratios in both dosage groups. It is difficult to assess the significance of the changes in the drug to metabolite ratios with time, since there are no kinetic data on the phase II metabolism (conjugation) of fluphenazine or fluphenazine sulfoxide. This study shows that sulfoxidation is an important major pathway in the metabolism of intramuscularly-administered fluphenazine, and implies that metabolic sites other than gut wall are also involved in the process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00187259
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of long-acting injectable neuroleptic drugs: clinical implications (1989)
    Springer
    Psychopharmacology 98 (1989), S. 433-439 
    Details
    ISSN: 1432-2072
    Keywords: Schizophrenia ; Neuroleptics ; Pharmacokinetics ; Long-acting neuroleptics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The authors review the literature regarding the pharmacokinetics of long-acting injectable neuroleptic drugs (LINS). There are important differences between LINS and oral neurolepties that affect their pharmacokinetics. By avoiding first pass metabolism in gut and liver, LINS result in lower circulating concentrations of metabolites than are found after oral administration. In addition, LINS take more time to reach a stable steady state than their oral counterparts. The clinical significance of these pharmacokinetic properties is discussed. The authors recommend that when patients are being changed from oral neuroleptics to LINS, that this conversion be done gradually over several months.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00441937
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Fluphenazine plasma levels in patients receiving low and conventional doses of fluphenazine decanoate (1986)
    Springer
    Psychopharmacology 88 (1986), S. 480-483 
    Details
    ISSN: 1432-2072
    Keywords: Schizophrenia ; Neuroleptic ; Fluphenazine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Plasma fluphenazine concentrations (FLU) were measured in 45 patients with schizophrenic disorders who participated in a double-blind comparison of 5 and 25 mg fluphenazine decanoate (FD). The rise in plasma level of FLU 24 h after a “test dose” was significantly correlated with steady state FLU concentration at 12 weeks (for 5 mg patients, r=0.45, P=0.04; for 25 mg, r=0.78, P=0.005). Patients who had low FLU at baseline required nearly 6 months to reach a steady state when they received 25 mg. Patients who received 5 mg and had low FLU at baseline continued to demonstrate relatively low plasma levels for the entire 1st year. Although the mean FLU at 6 months was lower for patients who relapsed during the subsequent 18 months (0.57 ng/ml for relapsers vs 1.01 ng/ml for nonrelapsers), this difference was not statistically significant. When plasma levels from both dosage groups were combined, FLU at 12 weeks correlated significantly with factor scores for akinesia (r=0.52, P=0.002) and BPRS cluster scores for retardation (r=0.52, P=0.002). These results indicate that the measurement of fluphenazine plasma levels may be useful in determining when patients treated with FD are receiving drug doses which are likely to cause discomforting side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00178510
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Distribution after repeated oral administration of different dose levels of risperidone and 9-hydroxy-risperidone in the brain and other tissues of rat (1998)
    Springer
    Psychopharmacology 139 (1998), S. 356-363 
    Details
    ISSN: 1432-2072
    Keywords: Key words Risperidone ; 9-Hydroxy-risperidone ; Antipsychotics ; Tissue distribution ; Regional brain distribution ; Brain to plasma level ratio ; Dose-tissue level relationship ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were treated with daily oral doses of 1, 4, and 6 mg/kg risperidone (RSP) and its metabolite, 9-hydroxy-risperidone (9-OH-RSP), for 15 consecutive days. Concentrations of RSP and 9-OH-RSP were measured in plasma, brain, liver, kidney, lungs and fat tissue by high-performance liquid chromatography with electrochemical detection. Non-specific distribution of RSP and 9-OH-RSP in various brain regions was also studied after administration of 6 mg/kg per day oral dose for 15 days. After RSP treatment, concentrations of 9-OH-RSP were higher than those of RSP in plasma and tissues except in brain, where both compounds were present in nearly equal concentrations. Similarly, after 9-OH-RSP treatment, levels of 9-OH-RSP were higher than levels of either RSP or 9-OH-RSP or the sum of RSP and 9-OH-RSP levels measured after treatment with RSP. There was a moderate relationship between RSP dose and tissue levels of RSP and 9-OH-RSP (all r s ≥ 0.62, P 〈 0.01), except in fat. There was also a strong relationship between the dose and tissue levels of 9-OH-RSP (all r s≥ 0.68, P 〈 0.005). A significant relationship was found between plasma levels of RSP and brain levels of RSP and 9-OH-RSP (all r s ≥ 0.57, P 〈 0.03) after treatment with RSP. After 9-OH-RSP treatment, a much stronger relationship was observed between plasma and brain 9-OH-RSP levels (r s ≥ 0.90, P 〈 0.005). The plasma concentrations of RSP and 9-OH-RSP appear to reflect their concentrations in brain. The tissue-to-plasma ratios of RSP and 9-OH-RSP were relatively low compared to other antipsychotics. In liver, kidney and lung the tissue to plasma ratio for RSP and 9-OH-RSP after treating with RSP ranged from 0.85 to 3.4. The brain to plasma ratio for RSP and 9-OH-RSP was several-fold lower than that in peripheral tissues. After RSP administration, the mean brain to plasma level ratio for RSP was 0.22, and for 9-OH-RSP to it was 0.04. The brain to plasma ratio of 9-OH-RSP after giving 9-OH-RSP was similarly low (0.04). The low brain/plasma ratio of high potency RSP and 9-OH-RSP may in part be due to their low lipophilicity, log P = 3.04 and 2.32, respectively, resulting in limited non-specific accumulation in brain tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050726
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  • 5
    Electronic Resource
    Electronic Resource
    Plasma levels of thiothixene by radioreceptor assay: Clinical usefulness (1983)
    Springer
    Psychopharmacology 79 (1983), S. 40-44 
    Details
    ISSN: 1432-2072
    Keywords: Radioreceptor assay ; Thiothixene plasma level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty-four newly admitted schizophrenic patients were treated with a fixed dose of thiothixene (0.44 mg/kg) for 4 weeks. Thiothixene and its active metabolites were measured by a new radioreceptor assay. Improvement occurred over the entire range of recorded plasma levels, but the chances of substantial improvement appear greater above 40 neuroleptic units (n.u.). The data do not support the notion of a “therapeutic window”, in that higher plasma levels were not associated with side effects or clinical deterioration (although at extreme plasma levels this must of course be so). In 11 non-responders dosage could not be increased because of side effects. If a non-responder with troublesome side effects has a low plasma level (〈40 n.u.), it would seem prudent to switch to another antipsychotic drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00433014
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  • 6
    Electronic Resource
    Electronic Resource
    Lithium attenuates the activation-euphoria but not the psychosis induced by d-amphetamine in schizophrenia (1985)
    Springer
    Psychopharmacology 87 (1985), S. 111-115 
    Details
    ISSN: 1432-2072
    Keywords: Lithium ; d-Amphetamine ; Activation ; Schizophrenia ; Psychosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract d-Amphetamine (20 mg) was administered intravenously in a double-blind design to 17 schizophrenic patients with and without concurrent 3-week lithium carbonate pretreatment to evaluate the lithium attenuation of d-amphetamine effects which we had observed in affective disorder patients. Lithium significantly attenuated the acute d-amphetamine-induced changes in an activation-euphoria cluster and in the mannerisms and posturing item of the Brief Psychiatric Rating Scale. Because the psychosis-increasing effects of d-amphetamine were not significantly decreased, it is conceivable that the d-amphetamine-induced changes in activation and euphoria and in psychosis are regulated by different dopamine mechanisms. The small clinical effects seen at 3 weeks of lithium treatment in schizophrenic patients could be mediated by dopamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431789
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    Paper (German National Licenses)
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