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Clive E Adams - One of the best experts on this subject based on the ideXlab platform.
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fluphenazine Decanoate depot and enanthate for schizophrenia
Cochrane Database of Systematic Reviews, 2015Co-Authors: Nicola Maayan, Seema N Quraishi, Aprajita Jayaswal, John Rathbone, Rosie Asher, Maurice Eisenbruch, Anthony S David, Clive E AdamsAbstract:Background Intramuscular injections (depot preparations) offer an advantage over oral medication for treating schizophrenia by reducing poor compliance. The benefits gained by long-acting preparations, however, may be offset by a higher incidence of adverse effects. Objectives To assess the effects of fluphenazine Decanoate and enanthate versus oral anti-psychotics and other depot neuroleptic preparations for individuals with schizophrenia in terms of clinical, social and economic outcomes. Search methods We searched the Cochrane Schizophrenia Group’s Trials Register (February 2011 and October 16, 2013), which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. Selection criteria We considered all relevant randomised controlled trials (RCTs) focusing on people with schizophrenia comparing fluphenazine Decanoate or enanthate with placebo or oral anti-psychotics or other depot preparations. Data collection and analysis We reliably selected, assessed the quality, and extracted data of the included studies. For dichotomous data, we estimated risk ratio (RR) with 95% confidence intervals (CI). Analysis was by intention-to-treat. We used the mean difference (MD) for normal continuous data. We excluded continuous data if loss to follow-up was greater than 50%. Tests of heterogeneity and for publication bias were undertaken. We used a fixed-effect model for all analyses unless there was high heterogeneity. For this update. we assessed risk of bias of included studies and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to create a 'Summary of findings' table. Main results This review now includes 73 randomised studies, with 4870 participants. Overall, the quality of the evidence is low to very low. Compared with placebo, use of fluphenazine Decanoate does not result in any significant differences in death, nor does it reduce relapse over six months to one year, but one longer-term study found that relapse was significantly reduced in the fluphenazine arm (n = 54, 1 RCT, RR 0.35, CI 0.19 to 0.64, very low quality evidence). A very similar number of people left the medium-term studies (six months to one year) early in the fluphenazine Decanoate (24%) and placebo (19%) groups, however, a two-year study significantly favoured fluphenazine Decanoate (n = 54, 1 RCT, RR 0.47, CI 0.23 to 0.96, very low quality evidence). No significant differences were found in mental state measured on the Brief Psychiatric Rating Scale (BPRS) or in extrapyramidal adverse effects, although these outcomes were only reported in one small study each. No study comparing fluphenazine Decanoate with placebo reported clinically significant changes in global state or hospital admissions. Fluphenazine Decanoate does not reduce relapse more than oral neuroleptics in the medium term (n = 419, 6 RCTs, RR 1.46 CI 0.75 to 2.83, very low quality evidence). A small study found no difference in clinically significant changes in global state. No difference in the number of participants leaving the study early was found between fluphenazine Decanoate (17%) and oral neuroleptics (18%), and no significant differences were found in mental state measured on the BPRS. Extrapyramidal adverse effects were significantly less for people receiving fluphenazine Decanoate compared with oral neuroleptics (n = 259, 3 RCTs, RR 0.47 CI 0.24 to 0.91, very low quality evidence). No study comparing fluphenazine Decanoate with oral neuroleptics reported death or hospital admissions. No significant difference in relapse rates in the medium term between fluphenazine Decanoate and fluphenazine enanthate was found (n = 49, 1 RCT, RR 2.43, CI 0.71 to 8.32, very low quality evidence), immediate- and short-term studies were also equivocal. One small study reported the number of participants leaving the study early (29% versus 12%) and mental state measured on the BPRS and found no significant difference for either outcome. No significant difference was found in extrapyramidal adverse effects between fluphenazine Decanoate and fluphenazine enanthate. No study comparing fluphenazine Decanoate with fluphenazine enanthate reported death, clinically significant changes in global state or hospital admissions. Authors' conclusions There are more data for fluphenazine Decanoate than for the enanthate ester. Both are effective antipsychotic preparations. Fluphenazine Decanoate produced fewer movement disorder effects than other oral antipsychotics but data were of low quality, and overall, adverse effect data were equivocal. In the context of trials, there is little advantage of these depots over oral medications in terms of compliance but this is unlikely to be applicable to everyday clinical practice.
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bromperidol Decanoate depot for schizophrenia
Cochrane Database of Systematic Reviews, 2012Co-Authors: Marianna Purgato, Clive E AdamsAbstract:BACKGROUND Antipsychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol Decanoate are extensively used as a means of long-term maintenance treatment. OBJECTIVES To assess the effects of depot bromperidol versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH METHODS For this 2012 update we searched the Cochrane Schizophrenia Group's Register (February 2012). SELECTION CRITERIA We sought all randomised trials focusing on people with schizophrenia where depot bromperidol, oral antipsychotics or other depot preparations. Primary outcomes were clinically significant change in global function, service utilisation outcomes (hospital admission, days in hospital), relapse. DATA COLLECTION AND ANALYSIS For the 2011 update MP independently extracted data, CEA carried out the reliability check. We calculated fixed-effect risk ratios (RR) and 95% confidence intervals (CI) for dichotomous data, and calculated weighted or standardised means for continuous data. Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat.For the 2012 update, data collection and analysis was not carried out as no new studies were found. MAIN RESULTS The 2012 search found no new studies, we have therefore included no new trials in this 2012 update. The number of included trials remain 4 RCTs, total n = 117. A single, small study of six months' duration compared bromperidol Decanoate with placebo injection. Similar numbers left the study before completion (n = 20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there were no clear differences between bromperidol Decanoate and placebo for a list of adverse effects (n = 20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69). When bromperidol Decanoate was compared with fluphenazine depot, we found no important change on global outcome (n = 30, RR no clinical important improvement 1.50 CI 0.29 to 7.73). People allocated to fluphenazine Decanoate and haloperidol Decanoate had fewer relapses than those given bromperidol Decanoate (n = 77, RR 3.92 Cl 1.05 to 14.60, NNH 6 CI 2 to 341). People allocated bromperidol Decanoate required additional antipsychotic medication somewhat more frequently than those taking fluphenazine Decanoate and haloperidol Decanoate, but the results did not reach conventional levels of statistical significance (n = 77, 2 RCTs, RR 1.72 CI 0.7 to 4.2). The use of benzodiazepine drugs was very similar in both groups (n = 77, 2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol Decanoate group more frequent than those taking other depot preparation due to any cause (n = 97, 3 RCTs, RR 2.17 CI 1.00 to 4.73). Anticholinergic adverse effects were equally common between bromperidol and other depots (n = 47, RR 3.13 CI 0.7 to 14.0) and additional anticholinergic medication was needed with equal frequency in both depot groups, although results did tend to favour the bromperidol Decanoate group (n = 97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders was similar in both depot groups (n = 77, 2 RCTs, RR 0.74 CI 0.47 to 1.17). AUTHORS' CONCLUSIONS Minimal poorly reported trial data suggests that bromperidol Decanoate may be better than placebo injection but less valuable than fluphenazine or haloperidol Decanoate. If bromperidol Decanoate is available it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol Decanoate. Well-conducted and reported randomised trials are needed to inform practice.
Moacir Wajner - One of the best experts on this subject based on the ideXlab platform.
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medium chain fatty acids accumulating in mcad deficiency elicit lipid and protein oxidative damage and decrease non enzymatic antioxidant defenses in rat brain
Neurochemistry International, 2009Co-Authors: Patricia Fernanda Schuck, Gustavo Da Costa Ferreira, Alana Pimentel Moura, Estela Natacha Brandt Busanello, Anelise Miotti Tonin, Carlos Severo Dutrafilho, Moacir WajnerAbstract:Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most frequent disorder of fatty acid oxidation with a similar prevalence to that of phenylketonuria. Affected patients present tissue accumulation of the medium-chain fatty acids octanoate (OA), Decanoate (DA) and cis-4-decenoate. Clinical presentation is characterized by neurological symptoms, such as convulsions and lethargy that may develop into coma and sudden death. The aim of the present work was to investigate the in vitro effect of OA and DA, the metabolites that predominantly accumulate in MCADD, on oxidative stress parameters in rat cerebral cortex homogenates. It was first verified that both DA and OA significantly increased chemiluminescence and thiobarbituric acid-reactive species levels (lipoperoxidation) and decreased the non-enzymatic antioxidant defenses, measured by the decreased total antioxidant capacity. DA also enhanced carbonyl content and oxidation of sulfhydryl groups (protein damage) and decreased reduced glutathione (GSH) levels. We also verified that DA-induced GSH decrease and sulfhydryl oxidation were not observed when cytosolic preparations (membrane-free supernatants) were used, suggesting a mitochondrial mechanism for these actions. Our present data show that the medium-chain fatty acids DA and OA that most accumulate in MCADD cause oxidative stress in rat brain. It is therefore presumed that this pathomechanism may be involved in the pathophysiology of the neurologic symptoms manifested by patients affected by MCADD.
Seema N Quraishi - One of the best experts on this subject based on the ideXlab platform.
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fluphenazine Decanoate depot and enanthate for schizophrenia
Cochrane Database of Systematic Reviews, 2015Co-Authors: Nicola Maayan, Seema N Quraishi, Aprajita Jayaswal, John Rathbone, Rosie Asher, Maurice Eisenbruch, Anthony S David, Clive E AdamsAbstract:Background Intramuscular injections (depot preparations) offer an advantage over oral medication for treating schizophrenia by reducing poor compliance. The benefits gained by long-acting preparations, however, may be offset by a higher incidence of adverse effects. Objectives To assess the effects of fluphenazine Decanoate and enanthate versus oral anti-psychotics and other depot neuroleptic preparations for individuals with schizophrenia in terms of clinical, social and economic outcomes. Search methods We searched the Cochrane Schizophrenia Group’s Trials Register (February 2011 and October 16, 2013), which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. Selection criteria We considered all relevant randomised controlled trials (RCTs) focusing on people with schizophrenia comparing fluphenazine Decanoate or enanthate with placebo or oral anti-psychotics or other depot preparations. Data collection and analysis We reliably selected, assessed the quality, and extracted data of the included studies. For dichotomous data, we estimated risk ratio (RR) with 95% confidence intervals (CI). Analysis was by intention-to-treat. We used the mean difference (MD) for normal continuous data. We excluded continuous data if loss to follow-up was greater than 50%. Tests of heterogeneity and for publication bias were undertaken. We used a fixed-effect model for all analyses unless there was high heterogeneity. For this update. we assessed risk of bias of included studies and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to create a 'Summary of findings' table. Main results This review now includes 73 randomised studies, with 4870 participants. Overall, the quality of the evidence is low to very low. Compared with placebo, use of fluphenazine Decanoate does not result in any significant differences in death, nor does it reduce relapse over six months to one year, but one longer-term study found that relapse was significantly reduced in the fluphenazine arm (n = 54, 1 RCT, RR 0.35, CI 0.19 to 0.64, very low quality evidence). A very similar number of people left the medium-term studies (six months to one year) early in the fluphenazine Decanoate (24%) and placebo (19%) groups, however, a two-year study significantly favoured fluphenazine Decanoate (n = 54, 1 RCT, RR 0.47, CI 0.23 to 0.96, very low quality evidence). No significant differences were found in mental state measured on the Brief Psychiatric Rating Scale (BPRS) or in extrapyramidal adverse effects, although these outcomes were only reported in one small study each. No study comparing fluphenazine Decanoate with placebo reported clinically significant changes in global state or hospital admissions. Fluphenazine Decanoate does not reduce relapse more than oral neuroleptics in the medium term (n = 419, 6 RCTs, RR 1.46 CI 0.75 to 2.83, very low quality evidence). A small study found no difference in clinically significant changes in global state. No difference in the number of participants leaving the study early was found between fluphenazine Decanoate (17%) and oral neuroleptics (18%), and no significant differences were found in mental state measured on the BPRS. Extrapyramidal adverse effects were significantly less for people receiving fluphenazine Decanoate compared with oral neuroleptics (n = 259, 3 RCTs, RR 0.47 CI 0.24 to 0.91, very low quality evidence). No study comparing fluphenazine Decanoate with oral neuroleptics reported death or hospital admissions. No significant difference in relapse rates in the medium term between fluphenazine Decanoate and fluphenazine enanthate was found (n = 49, 1 RCT, RR 2.43, CI 0.71 to 8.32, very low quality evidence), immediate- and short-term studies were also equivocal. One small study reported the number of participants leaving the study early (29% versus 12%) and mental state measured on the BPRS and found no significant difference for either outcome. No significant difference was found in extrapyramidal adverse effects between fluphenazine Decanoate and fluphenazine enanthate. No study comparing fluphenazine Decanoate with fluphenazine enanthate reported death, clinically significant changes in global state or hospital admissions. Authors' conclusions There are more data for fluphenazine Decanoate than for the enanthate ester. Both are effective antipsychotic preparations. Fluphenazine Decanoate produced fewer movement disorder effects than other oral antipsychotics but data were of low quality, and overall, adverse effect data were equivocal. In the context of trials, there is little advantage of these depots over oral medications in terms of compliance but this is unlikely to be applicable to everyday clinical practice.
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zuclopenthixol Decanoate for schizophrenia and other serious mental illnesses
Cochrane Database of Systematic Reviews, 1999Co-Authors: Evandro Silva Freire Coutinho, Seema N QuraishiAbstract:BACKGROUND There is a clear link between stopping antipsychotic medications and a relapse of psychotic symptoms. A series of long-acting intra-muscular preparations has been developed since the 1960s in the hope of reducing the frequency of relapse and, hence, overall disability. These depot preparations, active for weeks at a time, are frequently used for those who find taking oral medication on a regular basis difficult or unacceptable. It has, however, been a consistent concern that any reduction in relapse rate afforded by depot preparations may be offset by an increase in adverse effects such as drug-induced movement disorders. OBJECTIVES To compare zuclopenthixol Decanoate to oral zuclopenthixol and other antipsychotic preparations for the treatment of schizophrenia and similar serious mental illness. SEARCH STRATEGY Electronic searches of Biological Abstracts (1982-1998), CINAHL (1982-1998), The Cochrane Library (Issue 2, 1998), The Cochrane Schizophrenia Group's Register (April 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) were searched. References of all eligible studies were searched for further trials. The manufacturer of zuclopenthixol was contacted. SELECTION CRITERIA Inclusion criteria were that the clinical study should be randomised, focus on people with schizophrenia or other serious mental illness with psychotic symptoms, and compare the use of zuclopenthixol Decanoate to oral zuclopenthixol or other antipsychotic preparations. DATA COLLECTION AND ANALYSIS Data was extracted independently by two reviewers (EC, MF). Authors of trials were contacted for additional and missing data. Odds ratios (ORs) and 95% confidence intervals (CIs) of homogenous dichotomous data were calculated with the Peto method. Where possible the number needed to treat (NNT) and its 95% confidence interval was also calculated. MAIN RESULTS Four studies relating to zuclopenthixol Decanoate were included. All compared zuclopenthixol Decanoate with other depot preparations. Zuclopenthixol Decanoate prevented or postponed relapses when compared to other depots (NNT 8, CI 5-53). However, zuclopenthixol Decanoate may induce more adverse effects (NNH 5, CI 3-31) although it decreases need for anticholinergic medication when compared to a group of other depot preparations (NNT 9, CI 5-38). For the risk of leaving the study early, there was also a trend for benefit to those allocated to zuclopenthixol Decanoate. None of the studies reported outcomes on service utilisation, costs, or quality of life. REVIEWER'S CONCLUSIONS Choice of which depot to use must always take into account clinical judgement and the preferences of the recipients of care and their carers. Limited trial data suggests, however, that there are real differences between zuclopenthixol Decanoate and other depots and these differences largely favour the former. This review highlights the need for good controlled clinical trials to fully address the effects of zuclopenthixol Decanoate for those with schizophrenia. Future studies should report service utilisation data, as well as satisfaction with care and economic outcomes. Duration of such trials should be of a longer duration than the included studies (12 months or more).
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depot haloperidol Decanoate for schizophrenia
Cochrane Database of Systematic Reviews, 1999Co-Authors: Seema N Quraishi, Anthony S David, Marco Antonio Alves Brasil, Flavio Valdozende AlheiraAbstract:Background The mainstay of treatment for schizophrenia is the antipsychotic group of drugs. These are usually given orally but compliance with medication given by this route may be difficult to quantify. Problems with treatment adherence are common. The development of depot injections in the 1960s gave rise to their extensive use as a means of long-term maintenance treatment. Haloperidol Decanoate is one depot drug available in clinical practice. Objectives To assess the effects of haloperidol Decanoate versus oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. Search strategy Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane Schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). References of all identified trials were also inspected for more studies. Selection criteria All relevant randomised trials focusing on people with schizophrenia where haloperidol Decanoate, oral anti-psychotics or other depot preparations were compared. Outcomes such as death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment were sought. Data collection and analysis Studies were reliably selected, quality rated and data extracted. For dichotomous data Mantel-Haenszel odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. Main results In a haloperidol Decanoate versus placebo comparison, two small studies reported that significantly fewer people on depot left early (OR 0.09 CI 0.03-0.21, NNT 2 CI 1-3) or experienced no important improvement in mental state (OR 0. 04 CI 0.01-0.15). Zississ (1982) suggested that those taking haloperidol Decanoate would need less additional antipsychotic medication (OR 0.14 Cl 0.04-0.55, NNT 2 CI 1-5). Haloperidol Decanoate was compared to oral haloperidol in a single trial that showed no differences in global impression, mental state or side effects ( approximately approximately Zuardi 1983 approximately approximately , n=22). Compliance with medication was not reported in this study. Eight trials compared haloperidol Decanoate to other depot neuroleptics and again no differences were found for the outcomes of death, global impression, mental state, behaviour, or side effects. Reviewer's conclusions Haloperidol Decanoate may have a substantial effect in improving the symptoms and behaviour associated with schizophrenia in comparison to placebo, but data are remarkably sparse. There are no discernible differences between the depot form of haloperidol and its oral equivalent. For those needing and willing to take the drug, the means of administration is then a matter of individual choice and clinical judgement. As there are no clear differences between haloperidol Decanoate and other depots, the choice of depot medication could also be individually tailored and patient preference exercised. Well-conducted and reported randomised trials are needed comparing haloperidol Decanoate with other depots but the comparison of haloperidol Decanoate to oral antipsychotics is a priority.
Kamal K. Midha - One of the best experts on this subject based on the ideXlab platform.
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sensitive method for the simultaneous measurement of fluphenazine Decanoate and fluphenazine in plasma by high performance liquid chromatography with cuolometric detection
Journal of Chromatography B: Biomedical Sciences and Applications, 1997Co-Authors: J W Hubbard, Kamal K. MidhaAbstract:Abstract A highly sensitive and specific high-performance liquid chromatographic method with coulometric detection was developed for the simultaneous assay of fluphenazine Decanoate and fluphenazine in plasma. The extraction and sample clean-up procedures are simple, rapid to execute, yet yield chromatograms relatively free of any interference from endogenous plasma constituents, such that the extraordinary sensitivity of the coulometric detector can be exploited fully. This is the first analytical procedure for the simultaneous determination of fluphenazine Decanoate and fluphenazine. The detection limits for both fluphenazine Decanoate and fluphenazine were 0.1 ng/ml plasma and the limits of quantitation were 0.25 ng/ml plasma. Standard curves from 0.25 to 10 ng/ml were linear with coefficients of variation
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the role of the lymphatic system in the presystemic absorption of fluphenazine after intramuscular administration of fluphenazine Decanoate in rats
European Journal of Pharmaceutical Sciences, 1995Co-Authors: Y. Huang, J W Hubbard, Kamal K. MidhaAbstract:Abstract Sprague Dawley rats (n = 16) were injected intramuscularly with fluphenazine Decanoate (78 mg/kg) in sesame oil. Groups of four rats were surgically prepared on days 1, 7, 15 and 32 post-injection and samples of lymph obtained from the thoracic duct. Fluphenazine was found in similar concentrations in lymph and plasma, although the Decanoate was not detected in either body fluid. These data suggest that the lymphatic system plays a role in the presystemic absorption of fluphenazine after i.m. administration of fluphenazine Decanoate in the rat. In vitro experiments showed that fluphenazine Decanoate was very rapidly hydrolyzed when incubated with rat plasma ( t 1 2 0.6 h ) or muscle homogenates ( t 1 2 1.0 h ). Rates of hydrolysis of fluphenazine Decanoate were lower in dog muscle homogenates ( t 1 2 4.3 h ), and very much lower when incubated with plasma from dog 42.9 h) or humans ( t 1 2 50.9 h).
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plasma levels of fluphenazine in patients receiving fluphenazine Decanoate relationship to clinical response
British Journal of Psychiatry, 1991Co-Authors: Stephen R. Marder, T Van Putten, Manickam Aravagiri, E M Hawes, J W Hubbard, Kamal K. Midha, Gordon Mckay, Jim MintzAbstract:The levels of fluphenazine and fluphenazine sulphoxide in schizophrenic patients who were randomly assigned to receive either 5 mg or 25 mg of fluphenazine Decanoate every two weeks were monitored. Patients treated with 25 mg of fluphenazine Decanoate required three months to reach a steady-state plasma level, indicating that those patients who are being converted from oral to depot fluphenazine should continue to receive oral supplementation during the first three months of treatment with fluphenazine Decanoate. Plasma levels of fluphenazine sulphoxide were lower than levels of fluphenazine. At six and nine months following randomisation, there was a statistically significant relationship between lower fluphenazine plasma levels and an increased risk of psychotic exacerbations. A relatively weak relationship was found between fluphenazine plasma levels and akinesia, but non-significant relationships between fluphenazine levels and other neurological side-effects including akathisia, retardation, and tardive dyskinesia. Monitoring the plasma levels may be helpful to clinicians who are attempting to treat stabilised patients with the lowest effective dose of fluphenazine Decanoate.
J W Hubbard - One of the best experts on this subject based on the ideXlab platform.
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sensitive method for the simultaneous measurement of fluphenazine Decanoate and fluphenazine in plasma by high performance liquid chromatography with cuolometric detection
Journal of Chromatography B: Biomedical Sciences and Applications, 1997Co-Authors: J W Hubbard, Kamal K. MidhaAbstract:Abstract A highly sensitive and specific high-performance liquid chromatographic method with coulometric detection was developed for the simultaneous assay of fluphenazine Decanoate and fluphenazine in plasma. The extraction and sample clean-up procedures are simple, rapid to execute, yet yield chromatograms relatively free of any interference from endogenous plasma constituents, such that the extraordinary sensitivity of the coulometric detector can be exploited fully. This is the first analytical procedure for the simultaneous determination of fluphenazine Decanoate and fluphenazine. The detection limits for both fluphenazine Decanoate and fluphenazine were 0.1 ng/ml plasma and the limits of quantitation were 0.25 ng/ml plasma. Standard curves from 0.25 to 10 ng/ml were linear with coefficients of variation
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sensitive method for the simultaneous measurement of fluphenazine Decanoate and fluphenazine in plasma by high performance liquid chromatography with coulometric detection
Journal of Chromatography B: Biomedical Sciences and Applications, 1997Co-Authors: Jiangping Luo, J W Hubbard, K K MidhaAbstract:A highly sensitive and specific high-performance liquid chromatographic method with coulometric detection was developed for the simultaneous assay of fluphenazine Decanoate and fluphenazine in plasma. The extraction and sample clean-up procedures are simple, rapid to execute, yet yield chromatograms relatively free of any interference from endogenous plasma constituents, such that the extraordinary sensitivity of the coulometric detector can be exploited fully. This is the first analytical procedure for the simultaneous determination of fluphenazine Decanoate and fluphenazine. The detection limits for both fluphenazine Decanoate and fluphenazine were 0.1 ng/ml plasma and the limits of quantitation were 0.25 ng/ml plasma. Standard curves from 0.25 to 10 ng/ml were linear with coefficients of variation < 10%. The method was applied to measure plasma levels of fluphenazine Decanoate and fluphenazine in patients under medication with 25-50 mg biweekly intramuscular (i.m.) injections of fluphenazine Decanoate. It was possible to monitor the plasma levels of fluphenazine in all cases. Fluphenazine Decanoate was present in measurable concentration in the plasma of 4 out of 5 patients who received biweekly i.m. injections of 50 mg fluphenazine Decanoate. In a pilot experiment with a dog, the method was used to follow fluphenazine Decanoate and fluphenazine plasma levels up to 13 days, at least, after i.m. single dose (10 mg/kg).
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the role of the lymphatic system in the presystemic absorption of fluphenazine after intramuscular administration of fluphenazine Decanoate in rats
European Journal of Pharmaceutical Sciences, 1995Co-Authors: Y. Huang, J W Hubbard, Kamal K. MidhaAbstract:Abstract Sprague Dawley rats (n = 16) were injected intramuscularly with fluphenazine Decanoate (78 mg/kg) in sesame oil. Groups of four rats were surgically prepared on days 1, 7, 15 and 32 post-injection and samples of lymph obtained from the thoracic duct. Fluphenazine was found in similar concentrations in lymph and plasma, although the Decanoate was not detected in either body fluid. These data suggest that the lymphatic system plays a role in the presystemic absorption of fluphenazine after i.m. administration of fluphenazine Decanoate in the rat. In vitro experiments showed that fluphenazine Decanoate was very rapidly hydrolyzed when incubated with rat plasma ( t 1 2 0.6 h ) or muscle homogenates ( t 1 2 1.0 h ). Rates of hydrolysis of fluphenazine Decanoate were lower in dog muscle homogenates ( t 1 2 4.3 h ), and very much lower when incubated with plasma from dog 42.9 h) or humans ( t 1 2 50.9 h).
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plasma levels of fluphenazine in patients receiving fluphenazine Decanoate relationship to clinical response
British Journal of Psychiatry, 1991Co-Authors: Stephen R. Marder, T Van Putten, Manickam Aravagiri, E M Hawes, J W Hubbard, Kamal K. Midha, Gordon Mckay, Jim MintzAbstract:The levels of fluphenazine and fluphenazine sulphoxide in schizophrenic patients who were randomly assigned to receive either 5 mg or 25 mg of fluphenazine Decanoate every two weeks were monitored. Patients treated with 25 mg of fluphenazine Decanoate required three months to reach a steady-state plasma level, indicating that those patients who are being converted from oral to depot fluphenazine should continue to receive oral supplementation during the first three months of treatment with fluphenazine Decanoate. Plasma levels of fluphenazine sulphoxide were lower than levels of fluphenazine. At six and nine months following randomisation, there was a statistically significant relationship between lower fluphenazine plasma levels and an increased risk of psychotic exacerbations. A relatively weak relationship was found between fluphenazine plasma levels and akinesia, but non-significant relationships between fluphenazine levels and other neurological side-effects including akathisia, retardation, and tardive dyskinesia. Monitoring the plasma levels may be helpful to clinicians who are attempting to treat stabilised patients with the lowest effective dose of fluphenazine Decanoate.
