Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects

Gerrits, Mireille; Greef, Rik de; Peeters, Pierre

doi:10.1002/bdd.718

Cited by 26 publications

(19 citation statements)

References 9 publications

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“…Drinking water sooner than 10 minutes after administration of sublingual asenapine can reduce its bioavailability,2,26 with a 19% reduction in plasma exposure observed following water administration at two minutes. If placed elsewhere in the oral cavity, asenapine will still be absorbed, as demonstrated in an open-label, randomized, three-way crossover trial among healthy men who received single 5 mg doses of asenapine via sublingual, supralingual, and buccal routes,29 where with buccal administration (ie, “cheeking”) the plasma level exposure was almost 25% higher than for the sublingual route, and 6% lower with supralingual administration than with sublingual administration. These differences in exposure are smaller than the overall variability observed in studies, where overall exposure varied by 37%, with a mean interindividual variability of 26% and a mean intraindividual variability of 26% 26.…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

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Role of sublingual asenapine in treatment of schizophrenia

Citrome¹

2011

NDT

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Asenapine tablets are a new option for the treatment of schizophrenia. Sublingual administration is essential because bioavailability if ingested is less than 2%. Efficacy is supported by acute and long-term randomized controlled studies conducted by the manufacturer, with asenapine 5 mg twice daily evidencing superiority over placebo in six-week studies of acute schizophrenia, and flexibly-dosed asenapine (modal dose 10 mg twice daily) superior to placebo in a 26-week maintenance of response study. Tolerability advantages over some second-generation antipsychotics, such as olanzapine, include a relatively favorable weight and metabolic profile, as demonstrated in a 52-week randomized, head-to-head, double-blind clinical trial. Although dose-related extrapyramidal symptoms and akathisia can be present, the frequency of these effects is lower than that for haloperidol and risperidone. Somnolence may also occur, and appears to be somewhat dose-dependent when examining rates of this among patients receiving asenapine for schizophrenia and bipolar disorder. Prolactin elevation can occur, but at a rate lower than that observed for haloperidol or risperidone. Unique to asenapine is the possibility of oral hypoesthesia, occurring in about 5% of participants in the clinical trials. Obstacles to the use of asenapine are the recommendations for twice-daily dosing and the need to avoid food or liquids for 10 minutes after administration, although the bioavailability is only minimally reduced if food or liquids are avoided for only two minutes.

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Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

“…Directly asking patients about adverse effects, such as oral hypoesthesia, may yield higher rates. In healthy male subjects from a Phase I study of asenapine 5 mg,29 the most common adverse events were oral paresthesia (sublingual, 75.8%; supralingual, 55.9%; buccal, 45.7%) and somnolence (81.8%; 76.5%; 68.6%).…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Role of sublingual asenapine in treatment of schizophrenia

Citrome¹

2011

NDT

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“…For this reason, the manufacturer’s insert recommends that patients not eat or drink anything within 10 minutes following administration of the drug. However, Gerrits et al 15 has shown that consuming water at 5 minutes following a 5 mg dose of asenapine decreased the plasma levels by only 10%, and that consuming water 2 minutes following a similar dose lowered drug exposure by approximately 20%. 13 It is not likely that these differences in drug exposure are clinically meaningful, as the reductions in exposure are actually less than the mean interindividual exposure variability which is as high as 26% when administered with perfect adherence to US Food and Drug Administration (FDA) guidelines.…”

Section: Pharmacologymentioning

confidence: 99%

Asenapine for bipolar disorder

Scheidemantel¹,

Korobkova²,

Rej³

et al. 2015

NDT

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Asenapine (Saphris®) is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD). Data from randomized, double-blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be similarly modest. Asenapine does not appear to cause any clinically significant QTc prolongation. The most commonly reported extra-pyramidal symptom associated with asenapine was akathisia. Overall, asenapine appears to be a relatively well-tolerated atypical antipsychotic, effective in the treatment of acute manic and mixed episodes of BD.

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“…At doses above the saturation solubility, bioavailability becomes dependent on the distribution equilibrium and also on contact time in the mouth 57. Compared with the sublingual route, asenapine exposure is 24% higher with buccal and supralingual administration administration 58. However, the latter routes convey a risk of tooth decay.…”

Section: Review Of Pharmacology Mode Of Action and Pharmacokineticsmentioning

confidence: 99%

New approaches for the management of bipolar disorder: role of sublingual asenapine in the treatment of mania

Warren¹,

Dubovsky²

2013

NDT

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Bipolar disorder is a prevalent disorder that tends to become progressive without treatment and with inadequate treatment. Second generation (atypical) antipsychotic drugs have increasingly been used as adjunctive treatment or monotherapy for mania, but they have the potential for significant adverse effects and their role in maintenance treatment remains unclear. Asenapine is a new atypical antipsychotic medication formulated in a sublingual preparation that has been studied for mania but not maintenance therapy. Evidence indicating efficacy, adverse effects, and potential benefits and drawbacks of using asenapine in the treatment of bipolar disorder based on currently available published data are summarized.

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Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects

Cited by 26 publications

References 9 publications

Role of sublingual asenapine in treatment of schizophrenia

Role of sublingual asenapine in treatment of schizophrenia

Asenapine for bipolar disorder

New approaches for the management of bipolar disorder: role of sublingual asenapine in the treatment of mania

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