Effect of food on the pharmacokinetics of lurasidone: results of two randomized, open‐label, crossover studies

Preskorn, Sheldon; Ereshefsky, Larry; Chiu, Yu-Yuan; Poola, Nagaraju; Loebel, Antony

doi:10.1002/hup.2338

Cited by 54 publications

(24 citation statements)

References 21 publications

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“…For this reason, it is more effectively absorbed when taken with food. 33 This effect is similar to that observed with ziprasidone. 34 , 35 In both cases a meal of approximately 350 calories for lurasidone and 500 calories for ziprasidone, maximizes and stabilizes absorption of the drug.…”

Section: Pharmacokinetics Pharmacodynamics and Pharmacologysupporting

confidence: 79%

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Management of bipolar I depression: clinical utility of lurasidone

Findlay

El-Mallakh

El‐Mallakh

2015

TCRM

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Lurasidone is a benzisothiazol derivative second-generation antipsychotic. It has been approved in the United States and Europe for treatment of acute schizophrenia and bipolar depression. In type I bipolar subjects, treatment with lurasidone monotherapy of adjunctive therapy to lithium or valproic acid with doses of 20 to 120 mg once daily with food, results in statistically and clinically significant reduction of depressive symptoms. Patients experience relatively few side effects, which include somnolence, akathisia, nausea, and other gastrointestinal upset. Dopamine related side effects, such as Parkinsonism and elevated prolactin, are rare and mild. Longer term safety data obtained in 6 months long, open continuation observation periods, suggest that metabolic related elevations in weight, glucose, and lipids are absent or minimal. The mechanism of action of lurasidone is not known, but the data are compatible with antagonism of the serotonin 7 receptor. Lurasidone is a new option for the treatment of bipolar depression with relatively few side effects.

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Section: Pharmacokinetics Pharmacodynamics and Pharmacologysupporting

confidence: 79%

“…Absorption is increased approximately two to three times, and maximal serum concentration is increased about three fold. 33 Once absorbed, lurasidone is highly plasma protein bound (99.8% is bound to albumin and α-1-glycoprotein). 36 …”

Section: Pharmacokinetics Pharmacodynamics and Pharmacologymentioning

confidence: 99%

Management of bipolar I depression: clinical utility of lurasidone

Findlay

El-Mallakh

El‐Mallakh

2015

TCRM

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“…Therefore, the estimated extracellular lurasidone concentrations during local perfusions of 0.3, 1, and 3 μM were 32, 108, and 324 nM, respectively. The estimated concentrations at 1 and 3 μM are in the range of a plasma concentration of about 200 nM during conventional dosing at 120 mg·day −1 (Preskorn, Ereshefsky, Chiu, Poola, & Loebel, ).…”

Section: Methodsmentioning

confidence: 99%

Lurasidone inhibits NMDA receptor antagonist‐induced functional abnormality of thalamocortical glutamatergic transmission via 5‐HT₇ receptor blockade

Okada

Fukuyama

Ueda

2019

British J Pharmacology

139

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Background and Purpose Lurasidone is an atypical mood‐stabilizing antipsychotic with a unique receptor‐binding profile, including 5‐HT7 receptor antagonism; however, the detailed effects of 5‐HT7 receptor antagonism on various transmitter systems relevant to schizophrenia, particularly the thalamo‐insular glutamatergic system and the underlying mechanisms, are yet to be clarified. Experimental Approach We examined the mechanisms underlying the clinical effects of lurasidone by measuring the release of l‐glutamate, GABA, dopamine, and noradrenaline in the reticular thalamic nucleus (RTN), mediodorsal thalamic nucleus (MDTN) and insula of freely moving rats in response to systemic injection or local infusion of lurasidone or MK‐801 using multiprobe microdialysis with ultra‐HPLC. Key Results Systemic MK‐801 (0.5 mg·kg−1) administration increased insular release of l‐glutamate, dopamine, and noradrenaline but decreased GABA release. Systemic lurasidone (1 mg·kg−1) administration also increased insular release of l‐glutamate, dopamine, and noradrenaline but without affecting GABA. Local lurasidone administration into the insula (3 μM) did not affect MK‐801‐induced insular release of l‐glutamate or catecholamine, whereas local lurasidone administration into the MDTN (1 μM) inhibited MK‐801‐induced insular release of l‐glutamate and catecholamine, similar to the 5‐HT7 receptor antagonist SB269970. Conclusions and Implications The present results indicate that MK‐801‐induced insular l‐glutamate release is generated by activation of thalamo‐insular glutamatergic transmission via MDTN GABAergic disinhibition resulting from NMDA receptor inhibition in the MDTN and RTN. Lurasidone inhibited this MK‐801‐evoked insular l‐glutamate release through inhibition of excitatory 5‐HT7 receptor in the MDTN. These effects on thalamo‐insular glutamatergic transmission may contribute to the antipsychotic and mood‐stabilizing actions of lurasidone.

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“…The mean half-life at steady state is~33 h. Lurasidone is rapidly absorbed after oral administration, reaching peak serum concentrations in 1 --3 h. About 15% is absorbed on an empty stomach in comparison to a little more than twice that amount when ingested with food. Mean C max and AUC are approximately threefold and twofold, respectively, for administration of lurasidone with and without food [8]. The fat content of the meal has little effect and increasing the meal size beyond 350 calories has no impact.…”

Section: Pharmacokineticsmentioning

confidence: 95%

Lurasidone in the treatment of schizophrenia: a critical evaluation

Bruijnzeel

Yazdanpanah

Suryadevara

et al. 2015

Expert Opinion on Pharmacotherapy

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Lurasidone is a benzoisothiazole with potent dopamine D2 and serotonin 5HT2A antagonist and serotonin 5HT1A partial agonist properties (like other second-generation antipsychotic agents) with additional potent 5HT7 and alpha2C noradrenergic antagonism. It has little or no activity at the alpha1 and alpha2A noradrenergic, 5HT2C serotonergic, histaminergic and cholinergic receptors. Available only in an oral formulation, it is effective in once-daily dosing (40 - 160 mg/day) and its absorption is affected by food. There is an extensive clinical trial database with short-term and long-term placebo- and antipsychotic-controlled clinical trials evaluating the efficacy and safety/tolerability of lurasidone in the treatment of schizophrenia. It has been found to be efficacious with comparable efficacy to other agents in the treatment of acute psychosis and prevention of relapse in individuals with schizophrenia. The greater antidepressant and cognitive benefits suggested by its receptor profile need substantiation in robust clinical trials. It is less likely to cause metabolic and cardiac adverse effects than most other second-generation agents and is associated with a modest risk of extrapyramidal side-effects, akathisia, and prolactin elevation.

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Effect of food on the pharmacokinetics of lurasidone: results of two randomized, open‐label, crossover studies

Abstract: Lurasidone should be administered with food-at least 350 kcal-to ensure maximum exposure.

Cited by 54 publications

References 21 publications

Management of bipolar I depression: clinical utility of lurasidone

Management of bipolar I depression: clinical utility of lurasidone

Lurasidone inhibits NMDA receptor antagonist‐induced functional abnormality of thalamocortical glutamatergic transmission via 5‐HT₇ receptor blockade

Lurasidone in the treatment of schizophrenia: a critical evaluation

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Effect of food on the pharmacokinetics of lurasidone: results of two randomized, open‐label, crossover studies

Abstract: Lurasidone should be administered with food-at least 350 kcal-to ensure maximum exposure.

Cited by 54 publications

References 21 publications

Management of bipolar I depression: clinical utility of lurasidone

Management of bipolar I depression: clinical utility of lurasidone

Lurasidone inhibits NMDA receptor antagonist‐induced functional abnormality of thalamocortical glutamatergic transmission via 5‐HT7 receptor blockade

Lurasidone in the treatment of schizophrenia: a critical evaluation

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Lurasidone inhibits NMDA receptor antagonist‐induced functional abnormality of thalamocortical glutamatergic transmission via 5‐HT₇ receptor blockade