Asenapine: A Clinical Review of a Second-Generation Antipsychotic

Stoner, Steven C.; Pace, Heather A.

doi:10.1016/j.clinthera.2012.03.002

Cited by 32 publications

(17 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Age, BMI, race, and sex did not appear to be associated with clinically meaningful changes in asenapine exposure, suggesting that dose adjustments are not required based on these factors. Simulated C max and AUC 0–12 values for asenapine in the pediatric population are broadly similar to what has been reported in adults,2,21 indicating similar exposure at the same asenapine dose regardless of age.…”

Section: Discussionsupporting

confidence: 79%

Asenapine pharmacokinetics and tolerability in a pediatric population

Dogterom¹,

Riesenberg²,

Greef³

et al. 2018

DDDT

View full text Add to dashboard Cite

PurposeThis study aimed to characterize the pharmacokinetic (PK) properties, safety, and tolerability of asenapine, and to develop a population PK model in pediatric patients with schizophrenia, bipolar disorder, or other psychiatric disorders.MethodsTwo Phase I multiple ascending-dose studies were conducted to evaluate the PK, safety, and tolerability of sublingual asenapine in pediatric patients (age 10–17 years) with schizophrenia or bipolar I disorder. Patients received asenapine 1–10 mg twice daily for up to 12 days. PK parameters (maximum concentration [Cmax], area under the curve from 0 to 12 hours [AUC0–12], time to Cmax [Tmax], and half-life) were summarized for asenapine with descriptive statistics, and safety parameters were collected. A population PK model, which included the two Phase I studies and two additional Phase III efficacy studies (asenapine 2.5–10 mg twice daily for up to 8 weeks, age 10–17 years), was developed using nonlinear mixed-effect modeling based on a previously developed adult PK model. The final model was used in simulations to obtain asenapine-exposure estimates across pediatric subgroups and to determine if intrinsic covariates warrant dose adjustments.ResultsThe PK of asenapine showed rapid absorption (Tmax ~1 hour) with an apparent terminal half-life between 16 and 32 hours. Increases in mean Cmax and AUC0–12 appeared to be dose-proportional in one study and near dose-proportional in the second study. Steady state was attained within 8 days. The most frequently occurring treatment-emergent adverse events were dysgeusia, sedation, and oral hypoesthesia. Simulation-based estimates of Cmax and AUC0–12 were similar for pediatric and adult patients; age, body-mass index, race, and sex were not associated with changes in asenapine exposure.ConclusionAsenapine was generally safe and well tolerated in pediatric patients aged 10–17 years. PK and safety data were similar to that observed in the adult population. Intrinsic factors had no significant impact on asenapine exposure, indicating there is no need for dose adjustments in the pediatric population.

show abstract

Section: Discussionsupporting

confidence: 79%

Asenapine pharmacokinetics and tolerability in a pediatric population

Dogterom¹,

Riesenberg²,

Greef³

et al. 2018

DDDT

View full text Add to dashboard Cite

show abstract

“…The drug is currently approved for the acute and maintenance treatment of schizophrenia as well as for acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features as monotherapy or adjunctive medication along with lithium or valproate. Asenapine has a unique human receptor-binding profile characterized by an antagonistic action at serotonergic (5-HT 2 , 5-HT 5-7 ), adrenergic (α 1 and α 2 ), dopaminergic (D 1-4 ), and histaminergic H 1 receptors, but produces no action on the β-adrenergic or muscarinic receptors [8,9]. Due to its pharmacological profile, asenapine is effective not only against positive (psychotic) symptoms by affecting dopaminergic receptors, but it is also efficient against negative symptoms of schizophrenia improving mood and cognition (via 5-HT 1A , HT 2C , 5-HT 6 , and 5-HT 7 ), and simultaneously protecting against extrapyramidal symptoms (via 5-HT 2A ) [9,10].…”

Section: Introductionmentioning

confidence: 99%

In vitro inhibition of human cytochrome P450 enzymes by the novel atypical antipsychotic drug asenapine: a prediction of possible drug–drug interactions

et al. 2020

View full text Add to dashboard Cite

Background Inhibition of cytochrome P450 (CYP) enzymes is the most common cause of harmful drug-drug interactions. The present study aimed at examining the inhibitory effect of the novel antipsychotic drug asenapine on the main CYP enzymes in human liver. Methods The experiments were performed in vitro using pooled human liver microsomes and the human cDNA-expressed CYP enzymes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 (Supersomes). Activities of CYP enzymes were determined using the CYP-specific reactions: caffeine 3-N-demethylation (CYP1A2), diclofenac 4′-hydroxylation (CYP2C9), perazine N-demethylation (CYP2C19), bufuralol 1′-hydroxylation (CYP2D6), and testosterone 6β-hydroxylation (CYP3A4). The rates of the CYP-specific reactions were assessed in the absence and presence of asenapine using HPLC. Results The obtained results showed that both in human liver microsomes and Supersomes asenapine potently and to a similar degree inhibited the activity of CYP1A2 via a mixed mechanism (K i = 3.2 μM in liver microsomes and Supersomes) and CYP2D6 via a competitive mechanism (K i = 1.75 and 1.89 μM in microsomes and Supersomes, respectively). Moreover, asenapine attenuated the CYP3A4 activity via a non-competitive mechanism (K i = 31.3 and 27.3 μM in microsomes and Supersomes, respectively). In contrast, asenapine did not affect the activity of CYP2C9 or CYP2C19. Conclusion The potent inhibition of CYP1A2 and CYP2D6 by asenapine, demonstrated in vitro, will most probably be observed also in vivo, since the calculated K i values are close to the presumed concentration range for asenapine in the liver in vivo. Therefore, pharmacokinetic interactions involving asenapine and CYP2D6 or CYP1A2 substrates are likely to occur during their co-administration to patients.

show abstract

“…asenapine is registered for the treatment of acute and long-term schizophrenia in adults and for the acute treatment of manic or mixed episodes associated with BDI [8]. This was based on the results of several randomized controlled studies supporting its efficacy and good tolerability in both short-and long-term use in schizophrenic and BD patients in monotherapy [6,7,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] and in BDmixed episode [27][28][29]. The recommended dose of asenapine in monotherapy is 10 mg twice a day that can be reduced to 5 mg twice a day depending on the patient's response.…”

Section: Introductionmentioning

confidence: 99%