Peringatan Keamanan

Serdexmethylphenidate/dexmethylphenidate overdose results in symptoms consistent with CNS overstimulation, including gastrointestinal complaints such as nausea and vomiting, neurological effects including anxiety, euphoria, confusion, and hallucinations/delirium, cardiovascular effects such as arrhythmias, hypertension/hypotension, and tachycardia, general effects such as agitation, restlessness, twitching, convulsions, sweating, flushing, mucous membrane dryness, tachypnea, mydriasis, and serious effects such as rhabdomyolysis, loss of consciousness, coma, and death. Overdose treatment should consist of appropriate symptomatic and supportive care.L32298

Serdexmethylphenidate

DB16629

small molecule approved

Deskripsi

Attention Deficit Hyperactivity Disorder (ADHD) is an early-onset neurodevelopmental disorder that often extends into adulthood and is characterized by developmentally inappropriate and impaired attention, impulsivity, and motor hyperactivity.A230698, A230703 The underlying cause of ADHD is unclear but likely involves dysfunction in dopaminergic and noradrenergic neurotransmission, as evidenced by the clear beneficial effect of CNS stimulants such as methylphenidate and amphetamine that increase extracellular dopamine and norepinephrine levels.A230698, A230708 Serdexmethylphenidate is a prodrug of the CNS stimulant dexmethylphenidate, a common first-line treatment for ADHD, that is combined with dexmethylphenidate to provide extended plasma concentrations and therapeutic benefit with once-daily dosing.L32298, L32323

Serdexmethylphenidate was granted FDA approval on March 2, 2021, and is currently marketed as a combination capsule with dexmethylphenidate under the trademark AZSTARYS™ by KemPharm, Inc.

Struktur Molekul 2D

Berat 499.52
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Following a single oral dose of 52.3 mg/10.4 mg serdexmethylphenidate/dexmethylphenidate, the mean plasma terminal elimination half-lives of each component were roughly 5.7 and 11.7 hours, respectively.[L32298] At steady-state in healthy adults under fasted conditions, serdexmethylphenidate/dexmethylphenidate at 64/8, 56/12, and 48/16 mg resulted in a dexmethylphenidate half-life of between 8.5 ± 2.3 and 9.2 ± 3.5 hours.[L32323]
Volume Distribusi Serdexmethylphenidate has a mean apparent volume of distribution of 29.3 L/kg following serdexmethylphenidate/dexmethylphenidate administration.[L32298] Serdexmethylphenidate/dexmethylphenidate (28/6 or 56/12 mg) administered orally in patients aged between six and 17 years of age produced an apparent volume of distribution of dexmethylphenidate of between 37.6 and 66 L/kg.[L32328]
Klirens (Clearance) Serdexmethylphenidate has a mean apparent clearance of about 3.6 L/h/kg following oral serdexmethylphenidate/dexmethylphenidate administration.[L32298] In patients aged 6-17 years following oral administration of 28/6 or 56/12 mg serdexmethylphenidate/dexmethylphenidate, dexmethylphenidate has a mean apparent clearance of between 2.5 and 3.4 L/h/kg when normalized for dose.[L32328]

Absorpsi

Following a single dose of serdexmethylphenidate/dexmethylphenidate (52.3/10.4 mg) compared to extended-release dexmethylphenidate (40 mg) capsules in healthy volunteers under fasted conditions, the Cmax and AUC of dexmethylphenidate were 14.0 ng/mL and 186 ng\*h/mL and 28.2 ng/mL and 248 ng\*h/mL, respectively. The kinetics are approximately linear over a range of concentrations, with steady-state being reached after the third once-daily dose.L32298, L32333 Serdexmethylphenidate has a low oral bioavailability of 3%. The Tmax for both serdexmethylphenidate and dexmethylphenidate is approximately two hours under fasted conditions when coadministered. When serdexmethylphenidate is administered as a single entity, the dexmethylphenidate Tmax is approximately eight hours.L32298 Different ratios of serdexmethylphenidate to dexmethylphenidate, 64/8, 56/12, and 48/16 mg, each equivalent to 40 mg of dexmethylphenidate, were tested in healthy adult volunteers under fasted conditions. In each case, dexmethylphenidate reached peak plasma concentrations in roughly two hours (mean between 1.6-1.8 hours), which gradually decreased over 24 hours. The Cmax varied from 15.5 ± 3.7 to 23.8 ± 5.7 ng/mL while the AUC0-24h varied from 187.0 ± 41.0 to 207 ± 54.4 ng\*h/mL.L32323 Another study investigated the pharmacokinetics of serdexmethylphenidate/dexmethylphenidate (28/6 or 56/12 mg) in patients aged between six and 17 years of age. In general, the Cmax and AUC varied between cohorts and dose but were roughly equivalent when normalized for both dose and body weight.L32328

Metabolisme

Serdexmethylphenidate is converted to dexmethylphenidate in the lower gastrointestinal tract by as yet unknown enzymes. Following this, dexmethylphenidate is mainly converted to d-?-phenyl-piperidine acetic acid (d-ritalinic acid) in the liver by carboxylesterase 1A1.L32298, A176038 Other metabolites include the oxidation products 6-oxo-methylphenidate and p-hydroxy-methylphenidate, which are then de-esterified to oxo-ritalinic acid and p-hydroxy-ritalinic acid, respectively.A230743, A230748 Methylphenidate may also be trans-esterified to form ethylphenidate.A230748

Rute Eliminasi

Following oral serdexmethylphenidate dosing in humans, roughly 62% and 37% of the initial dose was recovered in the urine and feces, of which about 0.4% and 11% of the initial dose was recovered unchanged, respectively. Ritalinic acid accounted for approximately 63% of the recovered dose. When methylphenidate was administered orally as a racemate, about 90% of the dose was recovered in urine, of which racemic acid accounted for approximately 80% of the dose.L32298

Interaksi Makanan

1 Data
  • 1. Take with or without food. Food does not exert a clinically meaningful effect on dexmethylphenidate exposure, though it does lengthen the time to reach maximum plasma concentration from two hours to approximately 4-4.5 hours.

Interaksi Obat

545 Data
Desmopressin The risk or severity of hypertension can be increased when Desmopressin is combined with Serdexmethylphenidate.
Cyclosporine The risk or severity of hypertension can be increased when Cyclosporine is combined with Serdexmethylphenidate.
Icosapent The risk or severity of hypertension can be increased when Icosapent is combined with Serdexmethylphenidate.
Amphetamine The risk or severity of hypertension can be increased when Amphetamine is combined with Serdexmethylphenidate.
Phentermine The risk or severity of hypertension can be increased when Phentermine is combined with Serdexmethylphenidate.
Midodrine The risk or severity of hypertension can be increased when Midodrine is combined with Serdexmethylphenidate.
Eletriptan The risk or severity of hypertension can be increased when Eletriptan is combined with Serdexmethylphenidate.
Isoetharine The risk or severity of hypertension can be increased when Isoetharine is combined with Serdexmethylphenidate.
Mesalazine The risk or severity of hypertension can be increased when Mesalazine is combined with Serdexmethylphenidate.
Ziprasidone The risk or severity of hypertension can be increased when Ziprasidone is combined with Serdexmethylphenidate.
Methysergide The risk or severity of hypertension can be increased when Methysergide is combined with Serdexmethylphenidate.
Cabergoline The risk or severity of hypertension can be increased when Cabergoline is combined with Serdexmethylphenidate.
Atomoxetine The risk or severity of hypertension can be increased when Atomoxetine is combined with Serdexmethylphenidate.
Etomidate The risk or severity of hypertension can be increased when Etomidate is combined with Serdexmethylphenidate.
Zolmitriptan The risk or severity of hypertension can be increased when Zolmitriptan is combined with Serdexmethylphenidate.
Dihydroergotamine The risk or severity of hypertension can be increased when Dihydroergotamine is combined with Serdexmethylphenidate.
Amitriptyline The risk or severity of hypertension can be increased when Amitriptyline is combined with Serdexmethylphenidate.
Indomethacin The risk or severity of hypertension can be increased when Indomethacin is combined with Serdexmethylphenidate.
Protriptyline The risk or severity of hypertension can be increased when Protriptyline is combined with Serdexmethylphenidate.
Methylergometrine The risk or severity of hypertension can be increased when Methylergometrine is combined with Serdexmethylphenidate.
Clozapine The risk or severity of hypertension can be increased when Clozapine is combined with Serdexmethylphenidate.
Norepinephrine The risk or severity of hypertension can be increased when Norepinephrine is combined with Serdexmethylphenidate.
Mirtazapine The risk or severity of hypertension can be increased when Mirtazapine is combined with Serdexmethylphenidate.
Phenylephrine The risk or severity of hypertension can be increased when Phenylephrine is combined with Serdexmethylphenidate.
Phenylpropanolamine The risk or severity of hypertension can be increased when Phenylpropanolamine is combined with Serdexmethylphenidate.
Promazine The risk or severity of hypertension can be increased when Promazine is combined with Serdexmethylphenidate.
Methylphenidate The risk or severity of hypertension can be increased when Methylphenidate is combined with Serdexmethylphenidate.
Droperidol The risk or severity of hypertension can be increased when Droperidol is combined with Serdexmethylphenidate.
Imipramine The risk or severity of hypertension can be increased when Imipramine is combined with Serdexmethylphenidate.
Nabumetone The risk or severity of hypertension can be increased when Nabumetone is combined with Serdexmethylphenidate.
Ketorolac The risk or severity of hypertension can be increased when Ketorolac is combined with Serdexmethylphenidate.
Tenoxicam The risk or severity of hypertension can be increased when Tenoxicam is combined with Serdexmethylphenidate.
Chlorpromazine The risk or severity of hypertension can be increased when Chlorpromazine is combined with Serdexmethylphenidate.
Celecoxib The risk or severity of hypertension can be increased when Celecoxib is combined with Serdexmethylphenidate.
Buspirone The risk or severity of hypertension can be increased when Buspirone is combined with Serdexmethylphenidate.
Tolmetin The risk or severity of hypertension can be increased when Tolmetin is combined with Serdexmethylphenidate.
Rofecoxib The risk or severity of hypertension can be increased when Rofecoxib is combined with Serdexmethylphenidate.
Nortriptyline The risk or severity of hypertension can be increased when Nortriptyline is combined with Serdexmethylphenidate.
Amoxapine The risk or severity of hypertension can be increased when Amoxapine is combined with Serdexmethylphenidate.
Piroxicam The risk or severity of hypertension can be increased when Piroxicam is combined with Serdexmethylphenidate.
Doxapram The risk or severity of hypertension can be increased when Doxapram is combined with Serdexmethylphenidate.
Atropine The risk or severity of hypertension can be increased when Atropine is combined with Serdexmethylphenidate.
Fenoprofen The risk or severity of hypertension can be increased when Fenoprofen is combined with Serdexmethylphenidate.
Valdecoxib The risk or severity of hypertension can be increased when Valdecoxib is combined with Serdexmethylphenidate.
Diclofenac The risk or severity of hypertension can be increased when Diclofenac is combined with Serdexmethylphenidate.
Lisuride The risk or severity of hypertension can be increased when Lisuride is combined with Serdexmethylphenidate.
Sulindac The risk or severity of hypertension can be increased when Sulindac is combined with Serdexmethylphenidate.
Metaraminol The risk or severity of hypertension can be increased when Metaraminol is combined with Serdexmethylphenidate.
Dexmedetomidine The risk or severity of hypertension can be increased when Dexmedetomidine is combined with Serdexmethylphenidate.
Trazodone The risk or severity of hypertension can be increased when Trazodone is combined with Serdexmethylphenidate.
Epinephrine The risk or severity of hypertension can be increased when Epinephrine is combined with Serdexmethylphenidate.
Sumatriptan The risk or severity of hypertension can be increased when Sumatriptan is combined with Serdexmethylphenidate.
Thioridazine The risk or severity of hypertension can be increased when Thioridazine is combined with Serdexmethylphenidate.
Ergotamine The risk or severity of hypertension can be increased when Ergotamine is combined with Serdexmethylphenidate.
Nicergoline The risk or severity of hypertension can be increased when Nicergoline is combined with Serdexmethylphenidate.
Sufentanil The risk or severity of hypertension can be increased when Sufentanil is combined with Serdexmethylphenidate.
Flurbiprofen The risk or severity of hypertension can be increased when Flurbiprofen is combined with Serdexmethylphenidate.
Methoxamine The risk or severity of hypertension can be increased when Methoxamine is combined with Serdexmethylphenidate.
Trimipramine The risk or severity of hypertension can be increased when Trimipramine is combined with Serdexmethylphenidate.
Etodolac The risk or severity of hypertension can be increased when Etodolac is combined with Serdexmethylphenidate.
Propiomazine The risk or severity of hypertension can be increased when Propiomazine is combined with Serdexmethylphenidate.
Mefenamic acid The risk or severity of hypertension can be increased when Mefenamic acid is combined with Serdexmethylphenidate.
Naproxen The risk or severity of hypertension can be increased when Naproxen is combined with Serdexmethylphenidate.
Sulfasalazine The risk or severity of hypertension can be increased when Sulfasalazine is combined with Serdexmethylphenidate.
Alfentanil The risk or severity of hypertension can be increased when Alfentanil is combined with Serdexmethylphenidate.
Phenylbutazone The risk or severity of hypertension can be increased when Phenylbutazone is combined with Serdexmethylphenidate.
Fentanyl The risk or severity of hypertension can be increased when Fentanyl is combined with Serdexmethylphenidate.
Meloxicam The risk or severity of hypertension can be increased when Meloxicam is combined with Serdexmethylphenidate.
Orciprenaline The risk or severity of hypertension can be increased when Orciprenaline is combined with Serdexmethylphenidate.
Propofol The risk or severity of hypertension can be increased when Propofol is combined with Serdexmethylphenidate.
Carprofen The risk or severity of hypertension can be increased when Carprofen is combined with Serdexmethylphenidate.
Phenmetrazine The risk or severity of hypertension can be increased when Phenmetrazine is combined with Serdexmethylphenidate.
Trifluoperazine The risk or severity of hypertension can be increased when Trifluoperazine is combined with Serdexmethylphenidate.
Dobutamine The risk or severity of hypertension can be increased when Dobutamine is combined with Serdexmethylphenidate.
Pseudoephedrine The risk or severity of hypertension can be increased when Pseudoephedrine is combined with Serdexmethylphenidate.
Diflunisal The risk or severity of hypertension can be increased when Diflunisal is combined with Serdexmethylphenidate.
Benzphetamine The risk or severity of hypertension can be increased when Benzphetamine is combined with Serdexmethylphenidate.
Ritodrine The risk or severity of hypertension can be increased when Ritodrine is combined with Serdexmethylphenidate.
Terbutaline The risk or severity of hypertension can be increased when Terbutaline is combined with Serdexmethylphenidate.
Flupentixol The risk or severity of hypertension can be increased when Flupentixol is combined with Serdexmethylphenidate.
Remifentanil The risk or severity of hypertension can be increased when Remifentanil is combined with Serdexmethylphenidate.
Bitolterol The risk or severity of hypertension can be increased when Bitolterol is combined with Serdexmethylphenidate.
Quinidine The risk or severity of hypertension can be increased when Quinidine is combined with Serdexmethylphenidate.
Almotriptan The risk or severity of hypertension can be increased when Almotriptan is combined with Serdexmethylphenidate.
Oxymetazoline The risk or severity of hypertension can be increased when Oxymetazoline is combined with Serdexmethylphenidate.
Salicylic acid The risk or severity of hypertension can be increased when Salicylic acid is combined with Serdexmethylphenidate.
Diethylpropion The risk or severity of hypertension can be increased when Diethylpropion is combined with Serdexmethylphenidate.
Salmeterol The risk or severity of hypertension can be increased when Salmeterol is combined with Serdexmethylphenidate.
Meclofenamic acid The risk or severity of hypertension can be increased when Meclofenamic acid is combined with Serdexmethylphenidate.
Acetylsalicylic acid The risk or severity of hypertension can be increased when Acetylsalicylic acid is combined with Serdexmethylphenidate.
Naratriptan The risk or severity of hypertension can be increased when Naratriptan is combined with Serdexmethylphenidate.
Rizatriptan The risk or severity of hypertension can be increased when Rizatriptan is combined with Serdexmethylphenidate.
Formoterol The risk or severity of hypertension can be increased when Formoterol is combined with Serdexmethylphenidate.
Dopamine The risk or severity of hypertension can be increased when Dopamine is combined with Serdexmethylphenidate.
Oxaprozin The risk or severity of hypertension can be increased when Oxaprozin is combined with Serdexmethylphenidate.
Frovatriptan The risk or severity of hypertension can be increased when Frovatriptan is combined with Serdexmethylphenidate.
Albuterol The risk or severity of hypertension can be increased when Salbutamol is combined with Serdexmethylphenidate.
Ketoprofen The risk or severity of hypertension can be increased when Ketoprofen is combined with Serdexmethylphenidate.
Balsalazide The risk or severity of hypertension can be increased when Balsalazide is combined with Serdexmethylphenidate.
Ergoloid mesylate The risk or severity of hypertension can be increased when Ergoloid mesylate is combined with Serdexmethylphenidate.

Target Protein

Sodium-dependent dopamine transporter SLC6A3
Sodium-dependent noradrenaline transporter SLC6A2
5-hydroxytryptamine receptor 1A HTR1A

Referensi & Sumber

Synthesis reference: Travis Mickle, Sven M. Guenther, and Gouchen Chi, "Methylphenidate-prodrugs, processes of making and using the same." Patent WO2018107131A1, issued June 14, 2018.
Artikel (PubMed)
  • PMID: 26386541
    Thapar A, Cooper M: Attention deficit hyperactivity disorder. Lancet. 2016 Mar 19;387(10024):1240-50. doi: 10.1016/S0140-6736(15)00238-X. Epub 2015 Sep 17.
  • PMID: 31581854
    Childress AC, Komolova M, Sallee FR: An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations. Expert Opin Drug Metab Toxicol. 2019 Nov;15(11):937-974. doi: 10.1080/17425255.2019.1675636. Epub 2019 Nov 8.
  • PMID: 29428394
    Faraone SV: The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev. 2018 Apr;87:255-270. doi: 10.1016/j.neubiorev.2018.02.001. Epub 2018 Feb 8.
  • PMID: 19322953
    Markowitz JS, DeVane CL, Ramamoorthy S, Zhu HJ: The psychostimulant d-threo-(R,R)-methylphenidate binds as an agonist to the 5HT(1A) receptor. Pharmazie. 2009 Feb;64(2):123-5.
  • PMID: 17618619
    Riddle EL, Hanson GR, Fleckenstein AE: Therapeutic doses of amphetamine and methylphenidate selectively redistribute the vesicular monoamine transporter-2. Eur J Pharmacol. 2007 Sep 24;571(1):25-8. doi: 10.1016/j.ejphar.2007.05.044. Epub 2007 Jun 5.
  • PMID: 15999146
    Andrews GD, Lavin A: Methylphenidate increases cortical excitability via activation of alpha-2 noradrenergic receptors. Neuropsychopharmacology. 2006 Mar;31(3):594-601. doi: 10.1038/sj.npp.1300818.
  • PMID: 20855046
    Gamo NJ, Wang M, Arnsten AF: Methylphenidate and atomoxetine enhance prefrontal function through alpha2-adrenergic and dopamine D1 receptors. J Am Acad Child Adolesc Psychiatry. 2010 Oct;49(10):1011-23. doi: 10.1016/j.jaac.2010.06.015. Epub 2010 Sep 1.
  • PMID: 15082749
    Sun Z, Murry DJ, Sanghani SP, Davis WI, Kedishvili NY, Zou Q, Hurley TD, Bosron WF: Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther. 2004 Aug;310(2):469-76. doi: 10.1124/jpet.104.067116. Epub 2004 Apr 13.
Menampilkan 8 dari 10 artikel.

Contoh Produk & Brand

Produk: 3 • International brands: 0
Produk
  • Azstarys
    Capsule • - • Oral • US • Approved
  • Azstarys
    Capsule • - • Oral • US • Approved
  • Azstarys
    Capsule • - • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
© 2025 Digital Pharmacy Research - Universitas Esa Unggul