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James V. Cassella - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics and Safety of Single-Dose Inhaled Loxapine in Children and Adolescents.
Journal of clinical pharmacology, 2017Co-Authors: Sally Selim, James V. Cassella, Robert A Riesenberg, Jeevan Kunta, Edward T Hellriegel, Mark A Smith, Alexander A Vinks, Laura Rabinovich-guilattAbstract:This multisite open-label study sought to characterize the pharmacokinetics and safety of a single dose of inhaled Loxapine in children and adolescents. Loxapine powder for oral inhalation was administered via a single-use handheld drug device to children and adolescents (aged 10-17 years) with any condition warranting chronic antipsychotic use. Patients were dosed according to body weight and cohort (
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pharmacokinetics and safety of single dose inhaled Loxapine in children and adolescents
The Journal of Clinical Pharmacology, 2017Co-Authors: Sally Selim, James V. Cassella, Robert A Riesenberg, Jeevan Kunta, Edward T Hellriegel, Mark A Smith, Alexander A Vinks, Laura RabinovichguilattAbstract:This multisite open-label study sought to characterize the pharmacokinetics and safety of a single dose of inhaled Loxapine in children and adolescents. Loxapine powder for oral inhalation was administered via a single-use handheld drug device to children and adolescents (aged 10-17 years) with any condition warranting chronic antipsychotic use. Patients were dosed according to body weight and cohort (<50 kg [n = 15], 2.5 or 5 mg; ≥50 kg [n = 15], 5 or 10 mg); the first 6 patients (cohort 1) enrolled in each weight group received the lower dose. Patients were enrolled in the higher-dose group (cohort 2) after an interim pharmacokinetic and safety analysis of data from cohort 1. Blood samples were collected for 48 hours after dosing to determine the pharmacokinetic profile of Loxapine and its metabolites. Safety was assessed using adverse event (AE), laboratory value, physical/neurologic examination, vital sign, electrocardiogram, suicidality, and extrapyramidal symptom assessment. Thirty patients were enrolled and evaluable for pharmacokinetics. Loxapine plasma concentrations peaked by 2 to 5 minutes in most patients; systemic exposure increased with dose in both weight subgroups. Loxapine terminal elimination half-life was ∼13 to 17 hours. The most common AEs were sedation and dysgeusia. Sedation was severe in 1 patient in the <50-kg group (2.5-mg dose) and 1 patient in the ≥50-kg group (5-mg dose). No AEs indicative of bronchospasm or other serious AEs were reported. Inhaled Loxapine was rapidly absorbed and generally well tolerated in pediatric patients; no new safety signals were observed.
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ORIGINAL ARTICLE Effect of Smoking on the Pharmacokinetics of Inhaled Loxapine
2016Co-Authors: Lori H. Takahashi, Keith Huie, Daniel A. Spyker, Robert S Fishman, James V. CassellaAbstract:Background: Loxapine inhalation powder delivered by a hand-held device as a thermally generated aerosol (ADASUVE) was recently approved in the United States and European Union for use in the acute treatment of agitation in patients with bipolar disorder or schizophrenia. As smokers comprise a large subpopulation of these patients, and many antipsychotic drugs require dose adjust-ments for smokers, the objective of this study was to compare the pharmacokinetics of inhaled Loxapine administered to smokers and nonsmokers. Methods: Pharmacokinetics and sedation pharmacodynamics using a visual analog scale were studied in 35 male and female adult subjects (18 nonsmokers and 17 smokers) following a single dose of 10 mg of inhaled Loxapine. Blood samples were drawn a
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inhaled Loxapine and intramuscular lorazepam in healthy volunteers a randomized placebo controlled drug drug interaction study
Pharmacology Research & Perspectives, 2015Co-Authors: Daniel A. Spyker, James V. Cassella, Randall R Stoltz, Paul P YeungAbstract:Pharmacodynamic effects and safety of single-dose inhaled Loxapine administered via the Staccato(®) system and intramuscular (IM) lorazepam in combination versus each agent alone were compared in a randomized, double-blind, crossover study in healthy volunteers. Subjects received: inhaled Loxapine 10 mg + IM lorazepam 1 mg; inhaled Loxapine 10 mg + IM placebo; IM lorazepam 1 mg + Staccato placebo in random order, each separated by a 3-day washout. Primary endpoints were maximum effect (minimum value) and area under the curve (AUC) from baseline to 2 h post treatment for respirations/min and pulse oximetry. Least-squares means (90% confidence interval [CI]) for concomitant treatment versus each agent alone were derived and equivalence (no difference) confirmed if the 90% CI was within 0.8-1.25. Blood pressure (BP), heart rate (HR), sedation (100-mm visual analog scale), and adverse events (AEs) were recorded. All 18 subjects (mean age, 20.4 years; 61% male) completed the study. There was no difference between inhaled Loxapine + IM lorazepam and either agent alone on respiration or pulse oximetery during the 12-h postdose period, confirmed by 90% CIs for AUC and C min ratios. BP and HR were no different for inhaled Loxapine + IM lorazepam and each agent alone over a 12-h postdose period. Although the central nervous system sedative effects were observed for each treatment in healthy volunteers, the effect was greater following concomitant lorazepam 1 mg IM + inhaled Loxapine 10 mg administration. There were no deaths, serious AEs, premature discontinuations due to AEs, or treatment-related AEs.
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Multiple dose pharmacokinetics of inhaled Loxapine in subjects on chronic, stable antipsychotic regimens
Journal of clinical pharmacology, 2015Co-Authors: Daniel A. Spyker, Robert A Riesenberg, James V. CassellaAbstract:This randomized, double-blind, placebo-controlled, parallel-group study was to determine the pharmacokinetic characteristics, safety, and tolerability of multiple doses of inhaled Loxapine aerosol in subjects on a stable, oral, chronic antipsychotic regimen. Loxapine was delivered by means of a unique thermally generated aerosol comprising drug particles of a size designed for deep lung delivery and absorption. Thirty-two subjects were randomized 1:1:1:1 to receive inhaled Loxapine (total doses of 15, 20, or 30 mg) or inhaled placebo administered in 3 divided doses, given 4 hours apart. Following inhalation, the median Tmax was 2 minutes, and concentrations declined to about half Cmax approximately 5 minutes later across the 3 dose levels. The dose proportionality across data from this study combined with data from the single-dose study showed a slope (90%CI) of log AUCinf versus log dose of 0.818 (0.762–0.875) across the 8 doses (n = 60 subjects) studied, indicating reasonable dose proportionality. The most common adverse events were cough (3 of 32, 9%), sedation (3 of 32, 9%), and dysgeusia (2 of 32, 6%). The inhalation of multiple doses of inhaled Loxapine were well tolerated in study subjects and provided a safe, well-tolerated means for rapidly and reliably achieving therapeutic plasma concentrations of Loxapine. ClinicalTrials.gov identifier: NCT00555412
Shitij Kapur - One of the best experts on this subject based on the ideXlab platform.
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Contrasting Loxapine to its isomer isoLoxapine--the critical role of in vivo D2 blockade in determining atypicality.
Schizophrenia research, 2005Co-Authors: Sridhar Natesan, Suzi Vanderspek, José N Nobrega, Robert A Mcclelland, Shitij KapurAbstract:Loxapine is a typical antipsychotic while isoLoxapine, its 8Cl-isomer, shows atypicality in some animal models. The basis for this difference is not well understood. The purpose of this study was to systematically compare the two drugs in in vitro and in vivo animal models, and to understand mechanisms underlying their differential typical/atypical profiles. The in vitro and in vivo receptor profiles as well as the action of Loxapine and isoLoxapine on rat conditioned avoidance response (CAR), catalepsy (CAT), striatal FOS expression and prolactin levels were determined. To understand Loxapine's typical profile, we added MDL100,907, to provide Loxapine+MDL the same in vivo 5-HT2/D2 ratio as isoLoxapine, while holding its D2 component constant. IsoLoxapine behaved as an "atypical" antipsychotic demonstrating CAR inhibition, low CAT, no significant prolactin elevation, and minimal FOS expression in the dorsolateral striatum. Loxapine behaved like a typical antipsychotic, showing unexpectedly high in vivo D2 occupancy. Addition of MDL100,907, which resulted in a very high 5-HT2/D2 in vivo ratio, did not alter Loxapine + MDL's typical profile. Loxapine's behaviour as a typical antipsychotic is most likely due to its disproportionately high D2 occupancy. Appropriate action at D2 receptors in vivo, rather than the high 5-HT2/D2 ratio, seems to be critical in determining why isoLoxapine behaves like an atypical antipsychotic.
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contrasting Loxapine to its isomer isoLoxapine the critical role of in vivo d2 blockade in determining atypicality
Schizophrenia Research, 2005Co-Authors: Sridhar Natesan, Shitij Kapur, Suzi Vanderspek, José N Nobrega, Robert A McclellandAbstract:Abstract Background Loxapine is a typical antipsychotic while isoLoxapine, its 8Cl-isomer, shows atypicality in some animal models. The basis for this difference is not well understood. The purpose of this study was to systematically compare the two drugs in in vitro and in vivo animal models, and to understand mechanisms underlying their differential typical/atypical profiles. Methods The in vitro and in vivo receptor profiles as well as the action of Loxapine and isoLoxapine on rat conditioned avoidance response (CAR), catalepsy (CAT), striatal FOS expression and prolactin levels were determined. To understand Loxapine's typical profile, we added MDL100,907, to provide Loxapine + MDL the same in vivo 5-HT 2 / D 2 ratio as isoLoxapine, while holding its D 2 component constant. Results IsoLoxapine behaved as an “atypical” antipsychotic demonstrating CAR inhibition, low CAT, no significant prolactin elevation, and minimal FOS expression in the dorsolateral striatum. Loxapine behaved like a typical antipsychotic, showing unexpectedly high in vivo D 2 occupancy. Addition of MDL100,907, which resulted in a very high 5-HT 2 / D 2 in vivo ratio, did not alter Loxapine + MDL's typical profile. Conclusions Loxapine's behaviour as a typical antipsychotic is most likely due to its disproportionately high D 2 occupancy. Appropriate action at D 2 receptors in vivo, rather than the high 5-HT 2 / D 2 ratio, seems to be critical in determining why isoLoxapine behaves like an atypical antipsychotic.
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Contrasting Loxapine to its isomer isoLoxapine—the critical role of in vivo D2 blockade in determining atypicality
Schizophrenia Research, 2005Co-Authors: Sridhar Natesan, Suzi Vanderspek, José N Nobrega, Robert A Mcclelland, Shitij KapurAbstract:Abstract Background Loxapine is a typical antipsychotic while isoLoxapine, its 8Cl-isomer, shows atypicality in some animal models. The basis for this difference is not well understood. The purpose of this study was to systematically compare the two drugs in in vitro and in vivo animal models, and to understand mechanisms underlying their differential typical/atypical profiles. Methods The in vitro and in vivo receptor profiles as well as the action of Loxapine and isoLoxapine on rat conditioned avoidance response (CAR), catalepsy (CAT), striatal FOS expression and prolactin levels were determined. To understand Loxapine's typical profile, we added MDL100,907, to provide Loxapine + MDL the same in vivo 5-HT 2 / D 2 ratio as isoLoxapine, while holding its D 2 component constant. Results IsoLoxapine behaved as an “atypical” antipsychotic demonstrating CAR inhibition, low CAT, no significant prolactin elevation, and minimal FOS expression in the dorsolateral striatum. Loxapine behaved like a typical antipsychotic, showing unexpectedly high in vivo D 2 occupancy. Addition of MDL100,907, which resulted in a very high 5-HT 2 / D 2 in vivo ratio, did not alter Loxapine + MDL's typical profile. Conclusions Loxapine's behaviour as a typical antipsychotic is most likely due to its disproportionately high D 2 occupancy. Appropriate action at D 2 receptors in vivo, rather than the high 5-HT 2 / D 2 ratio, seems to be critical in determining why isoLoxapine behaves like an atypical antipsychotic.
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pet evidence that Loxapine is an equipotent blocker of 5 ht2 and d2 receptors implications for the therapeutics of schizophrenia
American Journal of Psychiatry, 1997Co-Authors: Shitij Kapur, Gordon Mckay, Gary Remington, Robert B Zipursky, C Jones, Sylvain HouleAbstract:OBJECTIVE: Loxapine, a dibenzoxazepine antipsychotic, is closely related to clozapine and shares clozapine's high affinity for binding to serotonin 5-HT2 and dopamine D4 receptors. The purpose of this study was to document Loxapine's 5-HT2 and D2 receptor occupancy in vivo in patients with psychoses. METHOD: Ten patients who were taking Loxapine (10–100 mg/day) had their D2 and 5-HT2 receptors assessed by means of positron emission tomography with [11C]raclopride and [18F]setoperone, respectively. RESULTS: The D2 receptor occupancy ranged from 43% to 90% 5-HT2 occupancy varied from 27% to near saturation. Statistical comparison of the results showed that Loxapine was equipotent in blocking 5-HT2 and D2 receptors. CONCLUSIONS: Loxapine differs from typical neuroleptics in demonstrating a high degree of 5-HT2 receptor occupancy. However, it is not “atypical” like clozapine and risperidone, since its 5-HT2 occupancy is not higher than its D2 occupancy. The results demonstrate that a high level of 5-HT2 occup...
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The D2 receptor occupancy profile of Loxapine determined using PET.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 1996Co-Authors: Shitij Kapur, Gary Remington, Robert B Zipursky, Corey Jones, Alan A. Wilson, Jean N. Dasilva, Sylvain HouleAbstract:Positron emission tomography (PET) studies of typical neuroleptics suggest that 60% to 80% of striatal D2 occupancy may be sufficient for optimal clinical treatment of psychosis. Therefore, striatal D2 occupancy may be used as an index to determine the optimal dose range. Toward this end, we determined the in vivo D2 profile of Loxapine, using [11C]-raclopride and PET. Seven patients selected from a clinical population were scanned while taking steady-state oral Loxapine from 10 to 100 mg/day. Their D2 receptor occupancy was estimated by comparing them to age-matched data from neuroleptic-naive patients. The D2 receptor occupancy ranged from 52% to 90%, and there was a very strong relationship between dose and D2 occupancy, suggesting that 15 to 30 mg/day of Loxapine would produce, the putatively optimal, 60% to 80% striatal D2 blockade. This dose range is much lower than that used in most clinical settings and points to the potential efficacy of Loxapine at lower doses.
Karuna Jayathilake - One of the best experts on this subject based on the ideXlab platform.
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Low-dose Loxapine in the treatment of schizophrenia: is it more effective and more "atypical" than standard-dose Loxapine?
The Journal of Clinical Psychiatry, 1999Co-Authors: Herbert Y. Meltzer, Karuna JayathilakeAbstract:Loxapine is chemically related to clozapine and shares with it and other atypical antipsychotic drugs relatively greater affinity for serotonin (5-HT) 2A than for dopamine D 2 receptors. However, as is the case for risperidone, the occupancy of 5-HT 2A and D 2 receptors can range from partial to full, depending upon the dose. It was, therefore, of interest to determine whether Loxapine at low doses ( 60 mg/day). We retrospectively examined data from 75 patients treated with Loxapine and found psychopathology data from 10 and 12 patients treated with low-dose or standard-dose Loxapine, respectively. No data were available on the other 53 patients, 28 of whom were initially treated with low-dose and 25 with standard-dose Loxapine. For those treated for at least 6 weeks, there was evidence of equivalent efficacy for both low- and standard-dose Loxapine with regard to improvement in Brief Psychiatric Rating Scale (BPRS) and Global Assessment Scale scores. There were 6 patients with a history of neuroleptic resistance among the 22 completers. Four of the low-dose group (40%) and 8 of the standard-dose group (67%) had at least a 20% decrease in BPRS total scores. Further study of the dose-response curve for Loxapine and its usefulness in treating neuroleptic-resistant schizophrenia is indicated.
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Low-dose Loxapine in the treatment of schizophrenia: is it more effective and more "atypical" than standard-dose Loxapine?
The Journal of clinical psychiatry, 1999Co-Authors: Herbert Y. Meltzer, Karuna JayathilakeAbstract:Loxapine is chemically related to clozapine and shares with it and other atypical antipsychotic drugs relatively greater affinity for serotonin (5-HT)2A than for dopamine D2 receptors. However, as is the case for risperidone, the occupancy of 5-HT2A and D2 receptors can range from partial to full, depending upon the dose. It was, therefore, of interest to determine whether Loxapine at low doses (< 50 mg/day) might be at least as or more effective and more tolerable than usual clinical doses (> or = 60 mg/day). We retrospectively examined data from 75 patients treated with Loxapine and found psychopathology data from 10 and 12 patients treated with low-dose or standard-dose Loxapine, respectively. No data were available on the other 53 patients, 28 of whom were initially treated with low-dose and 25 with standard-dose Loxapine. For those treated for at least 6 weeks, there was evidence of equivalent efficacy for both low- and standard-dose Loxapine with regard to improvement in Brief Psychiatric Rating Scale (BPRS) and Global Assessment Scale scores. There were 6 patients with a history of neuroleptic resistance among the 22 completers. Four of the low-dose group (40%) and 8 of the standard-dose group (67%) had at least a 20% decrease in BPRS total scores. Further study of the dose-response curve for Loxapine and its usefulness in treating neuroleptic-resistant schizophrenia is indicated.
Daniel A. Spyker - One of the best experts on this subject based on the ideXlab platform.
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ORIGINAL ARTICLE Effect of Smoking on the Pharmacokinetics of Inhaled Loxapine
2016Co-Authors: Lori H. Takahashi, Keith Huie, Daniel A. Spyker, Robert S Fishman, James V. CassellaAbstract:Background: Loxapine inhalation powder delivered by a hand-held device as a thermally generated aerosol (ADASUVE) was recently approved in the United States and European Union for use in the acute treatment of agitation in patients with bipolar disorder or schizophrenia. As smokers comprise a large subpopulation of these patients, and many antipsychotic drugs require dose adjust-ments for smokers, the objective of this study was to compare the pharmacokinetics of inhaled Loxapine administered to smokers and nonsmokers. Methods: Pharmacokinetics and sedation pharmacodynamics using a visual analog scale were studied in 35 male and female adult subjects (18 nonsmokers and 17 smokers) following a single dose of 10 mg of inhaled Loxapine. Blood samples were drawn a
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inhaled Loxapine and intramuscular lorazepam in healthy volunteers a randomized placebo controlled drug drug interaction study
Pharmacology Research & Perspectives, 2015Co-Authors: Daniel A. Spyker, James V. Cassella, Randall R Stoltz, Paul P YeungAbstract:Pharmacodynamic effects and safety of single-dose inhaled Loxapine administered via the Staccato(®) system and intramuscular (IM) lorazepam in combination versus each agent alone were compared in a randomized, double-blind, crossover study in healthy volunteers. Subjects received: inhaled Loxapine 10 mg + IM lorazepam 1 mg; inhaled Loxapine 10 mg + IM placebo; IM lorazepam 1 mg + Staccato placebo in random order, each separated by a 3-day washout. Primary endpoints were maximum effect (minimum value) and area under the curve (AUC) from baseline to 2 h post treatment for respirations/min and pulse oximetry. Least-squares means (90% confidence interval [CI]) for concomitant treatment versus each agent alone were derived and equivalence (no difference) confirmed if the 90% CI was within 0.8-1.25. Blood pressure (BP), heart rate (HR), sedation (100-mm visual analog scale), and adverse events (AEs) were recorded. All 18 subjects (mean age, 20.4 years; 61% male) completed the study. There was no difference between inhaled Loxapine + IM lorazepam and either agent alone on respiration or pulse oximetery during the 12-h postdose period, confirmed by 90% CIs for AUC and C min ratios. BP and HR were no different for inhaled Loxapine + IM lorazepam and each agent alone over a 12-h postdose period. Although the central nervous system sedative effects were observed for each treatment in healthy volunteers, the effect was greater following concomitant lorazepam 1 mg IM + inhaled Loxapine 10 mg administration. There were no deaths, serious AEs, premature discontinuations due to AEs, or treatment-related AEs.
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Multiple dose pharmacokinetics of inhaled Loxapine in subjects on chronic, stable antipsychotic regimens
Journal of clinical pharmacology, 2015Co-Authors: Daniel A. Spyker, Robert A Riesenberg, James V. CassellaAbstract:This randomized, double-blind, placebo-controlled, parallel-group study was to determine the pharmacokinetic characteristics, safety, and tolerability of multiple doses of inhaled Loxapine aerosol in subjects on a stable, oral, chronic antipsychotic regimen. Loxapine was delivered by means of a unique thermally generated aerosol comprising drug particles of a size designed for deep lung delivery and absorption. Thirty-two subjects were randomized 1:1:1:1 to receive inhaled Loxapine (total doses of 15, 20, or 30 mg) or inhaled placebo administered in 3 divided doses, given 4 hours apart. Following inhalation, the median Tmax was 2 minutes, and concentrations declined to about half Cmax approximately 5 minutes later across the 3 dose levels. The dose proportionality across data from this study combined with data from the single-dose study showed a slope (90%CI) of log AUCinf versus log dose of 0.818 (0.762–0.875) across the 8 doses (n = 60 subjects) studied, indicating reasonable dose proportionality. The most common adverse events were cough (3 of 32, 9%), sedation (3 of 32, 9%), and dysgeusia (2 of 32, 6%). The inhalation of multiple doses of inhaled Loxapine were well tolerated in study subjects and provided a safe, well-tolerated means for rapidly and reliably achieving therapeutic plasma concentrations of Loxapine. ClinicalTrials.gov identifier: NCT00555412
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safety and tolerability of inhaled Loxapine in subjects with asthma and chronic obstructive pulmonary disease two randomized controlled trials
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2014Co-Authors: Nicholas Gross, Daniel A. Spyker, Robert S Fishman, Leon S Greos, Eli O Meltzer, Selwyn Spangenthal, James V. CassellaAbstract:Abstract Background: Loxapine, a first-generation antipsychotic, delivered with a novel inhalation delivery device developed for the acute treatment of agitation in patients with schizophrenia or bipolar disorder was evaluated in subjects with asthma or chronic obstructive pulmonary disease (COPD). Methods: Separate randomized, double-blind, parallel-arm, placebo-controlled trials compared two administrations of inhaled Loxapine (10 mg) 10 hr apart with placebo in 52 subjects with asthma and in 53 subjects with COPD. A thermally-generated drug aerosol of Loxapine was delivered to the deep lung for rapid systemic absorption. Controller medications were continued throughout the study, but quick-relief bronchodilators were withheld from 6–8 hr before through 34 hr after dose 1, unless indicated as rescue. Results: All airway adverse events (AEs) were of mild or moderate severity. Symptomatic bronchospasm occurred in 53.8% of subjects with asthma after inhaled Loxapine and 11.5% after placebo; and in 19.2% of...
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Loxapine delivered as a thermally generated aerosol does not prolong qtc in a thorough qt qtc study in healthy subjects
The Journal of Clinical Pharmacology, 2014Co-Authors: Daniel A. Spyker, Polina Voloshko, Eugene R Heyman, James V. CassellaAbstract:The objective of this study was to establish effects of inhaled Loxapine on the QTc interval in this randomized, placebo-controlled, double-blind crossover study. Forty-eight healthy volunteers received a single inhaled placebo or 10 mg Loxapine. Plasma concentrations of Loxapine increased with a median Tmax of 1 minute and a mean Cmax of 312 ng/mL. After an initial rapid distribution phase, plasma concentrations of Loxapine declined with a terminal half-life of 8 hours. Exposure to the active metabolite 7-OH-Loxapine was 15% of the parent compound based on mean AUCinf and its terminal half-life was 12 hours. Inhaled Loxapine did not increase QT intervals, as demonstrated by the upper bound of the 1-sided 95% CIs placed on the point estimate of the placebo-subtracted change of QTcI (ΔΔQTcI) being less than 10 milliseconds at all 11 post-dose times. The maximum ΔΔQTcI occurred at 1 hour post-dose (LSmean 5.42 milliseconds, upper confidence bound 7.75 milliseconds). The study outcome was validated by the demonstrated assay sensitivity using the positive control moxifloxacin maximum ΔΔQTcI occurred at 3 hour post-dose (LSmean 8.36 milliseconds, lower confidence bound 5.82 milliseconds). The analyses of QTc outliers, and the lack of emergent diagnostic findings for QTcI, QTcB, and QTcF; and simple mean placebo-subtracted changes of QTcI and QTcF supported the primary QT analysis conclusion that this is a negative finding and there is no apparent QT prolongation associated with the therapeutic dose of inhaled Loxapine.
Herbert Y. Meltzer - One of the best experts on this subject based on the ideXlab platform.
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Low-dose Loxapine in the treatment of schizophrenia: is it more effective and more "atypical" than standard-dose Loxapine?
The Journal of Clinical Psychiatry, 1999Co-Authors: Herbert Y. Meltzer, Karuna JayathilakeAbstract:Loxapine is chemically related to clozapine and shares with it and other atypical antipsychotic drugs relatively greater affinity for serotonin (5-HT) 2A than for dopamine D 2 receptors. However, as is the case for risperidone, the occupancy of 5-HT 2A and D 2 receptors can range from partial to full, depending upon the dose. It was, therefore, of interest to determine whether Loxapine at low doses ( 60 mg/day). We retrospectively examined data from 75 patients treated with Loxapine and found psychopathology data from 10 and 12 patients treated with low-dose or standard-dose Loxapine, respectively. No data were available on the other 53 patients, 28 of whom were initially treated with low-dose and 25 with standard-dose Loxapine. For those treated for at least 6 weeks, there was evidence of equivalent efficacy for both low- and standard-dose Loxapine with regard to improvement in Brief Psychiatric Rating Scale (BPRS) and Global Assessment Scale scores. There were 6 patients with a history of neuroleptic resistance among the 22 completers. Four of the low-dose group (40%) and 8 of the standard-dose group (67%) had at least a 20% decrease in BPRS total scores. Further study of the dose-response curve for Loxapine and its usefulness in treating neuroleptic-resistant schizophrenia is indicated.
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Low-dose Loxapine in the treatment of schizophrenia: is it more effective and more "atypical" than standard-dose Loxapine?
The Journal of clinical psychiatry, 1999Co-Authors: Herbert Y. Meltzer, Karuna JayathilakeAbstract:Loxapine is chemically related to clozapine and shares with it and other atypical antipsychotic drugs relatively greater affinity for serotonin (5-HT)2A than for dopamine D2 receptors. However, as is the case for risperidone, the occupancy of 5-HT2A and D2 receptors can range from partial to full, depending upon the dose. It was, therefore, of interest to determine whether Loxapine at low doses (< 50 mg/day) might be at least as or more effective and more tolerable than usual clinical doses (> or = 60 mg/day). We retrospectively examined data from 75 patients treated with Loxapine and found psychopathology data from 10 and 12 patients treated with low-dose or standard-dose Loxapine, respectively. No data were available on the other 53 patients, 28 of whom were initially treated with low-dose and 25 with standard-dose Loxapine. For those treated for at least 6 weeks, there was evidence of equivalent efficacy for both low- and standard-dose Loxapine with regard to improvement in Brief Psychiatric Rating Scale (BPRS) and Global Assessment Scale scores. There were 6 patients with a history of neuroleptic resistance among the 22 completers. Four of the low-dose group (40%) and 8 of the standard-dose group (67%) had at least a 20% decrease in BPRS total scores. Further study of the dose-response curve for Loxapine and its usefulness in treating neuroleptic-resistant schizophrenia is indicated.
