Lompat ke isi

Setirizin

Dari Wikipedia bahasa Indonesia, ensiklopedia bebas
Revisi sejak 10 Juni 2020 07.13 oleh Riki.rinjani (bicara | kontrib) (←Membuat halaman berisi '{{short description|Antihistamine}} {{Use dmy dates|date=April 2020}} {{Drugbox | Watchedfields = changed <!--airbag--> | verifiedrevid = 460026203 | IUPAC_name =...')
(beda) ← Revisi sebelumnya | Revisi terkini (beda) | Revisi selanjutnya → (beda)

Setirizin
Nama sistematis (IUPAC)
(±)-[2-[4-[(4-Chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid
Data klinis
Nama dagang Zyrtec, Incidal, others
AHFS/Drugs.com monograph
MedlinePlus a698026
Data lisensi US Daily Med:pranala
Kat. kehamilan B2(AU) B(US)
Status hukum Unscheduled (AU) OTC (CA) GSL (UK) OTC (US) OTC
Rute By mouth
Data farmakokinetik
Bioavailabilitas Well-absorbed (>70%)[1]
Ikatan protein 88–96%[1]
Metabolisme Minimal (non-cytochrome P450-mediated)[2][3]
Waktu paruh Mean: 8.3 hours[2][3]
Range: 6.5–10 hours[4]
Ekskresi Urine: 70–85%[2]
Feces: 10–13%[2]
Pengenal
Nomor CAS 83881-51-0 YaY
Kode ATC R06AE07
PubChem CID 2678
Ligan IUPHAR 1222
DrugBank DB00341
ChemSpider 2577 YaY
UNII YO7261ME24 YaY
KEGG D07662 YaY
ChEBI CHEBI:3561 YaY
ChEMBL CHEMBL1000 YaY
Data kimia
Rumus C21H25ClN2O3 

  • InChI=1S/C21H25ClN2O3/c22-19-8-6-18(7-9-19)21(17-4-2-1-3-5-17)24-12-10-23(11-13-24)14-15-27-16-20(25)26/h1-9,21H,10-16H2,(H,25,26) YaY
    Key:ZKLPARSLTMPFCP-UHFFFAOYSA-N YaY

Cetirizine, dijual di pasaran dengan merek antara lain Incidal, adalah generasi kedua antihistamin yang digunakan untuk pengobatan rhinitis alergi (hay fever), dermatitis, dan urticaria.[5] Cetirizine dikonsumsi per oral.[6] Khasiat biasanya mulai muncul dalam waktu satu jam, dan biasanya bertahan selama satu hari.[6] Khasiat yang diberikan serupa dengan antihistamin lain seperti difenhidramin.[6]

Efek samping yang umum terjadi antara lain mengantuk, mulut kering, sakit kepala, dan nyeri pada abdominal.[6] Efek mengantuk biasanya tidak sekuat antihistamin generasi pertamas.[5] Efek samping yang lebih serius antara lain sikap agresif dan angioedema.[5] Penggunaan obat ini pada kehamilan tampaknya aman, sedangkan penggunaan selama menyusui tidak dianjurkan.[7] Obat ini bekerja dengan cara menghambat H1 reseptor histamin , terutama yang terletak di luar otak.[6]

Obat ini dipatentan ditahun 1981 dan mulai digunakan untuk pengobatan pada tahun 1987.[8] Obat ini tersedian dalam bentuk produk obat generik.[5] Harga obat ini untuk penggunaan selama satu bulan di Inggris Raya NHS sekitar £0.70 pada tahun 2019.[5], sedangkan di Amerika Serikat harganya sekitar US$2.50.[9] Pada tahun 2017, obat ini menempati peringkat ke 66 obat yang paling banyak diresepkan di Amerika Serikat, sekitar lebih dari sebelas juta resep.[10][11]

Penggunaan medis

Alergi

Indikasi utama Cetirizine adalah hay fever dan alergi lainnya. Karena gejala gatal dan kemerahan biasanya disebabkan oleh reaksi histamin pada reseptior H1, gejala akan hilang jika reseptor tersebut dihambat.

Cetirizine juga sering diresepkan untuk pengobatan urticaria akut dan terkadang kronik, dan memberikan hasil yang lebih efisien daripada antihistamin generasi kedua lainnya[butuh rujukan].

Available forms

Cetirizine dijual bebas di Amerika Serikat dalam bentuk tablet 5 mg dan 10 mg. Tablet 20 mg tersedia hanya melalui peresepan.[2] Di Inggris Raya, obat ini bisa dibeli paling banyak 30 tablet 10 mg tanpa resep.

Adverse effects

Efek samping yang sering ditemui antara lain sakit kepala, mulut kering, mengantuk, dan lemas, sedangkan efek yang jarang terjadi antara lain gagal jantung, takikardia, dan edema.[12]

Menghentikan penggunaan setelah penggunaan jangka panjang (biasanya melebihi enam bulan) bisa menyebabkan gatal.[13][14][15]

Pharmacology

L-Stereoisomer, levocetirizine (top) and D-stereoisomer of cetirizine.

Pharmacodynamics

Cetirizine bekerja sebagai antagonis selektif dari H1 reseptor histamin .[2] Nilai Ki values untuk reseptor H1 adalah 6 nM untuk cetirizine, 3 nM untuk levocetirizine, dan 100 nM untuk dextrocetirizine, menandakan bahwa levorotatory enantiomer adalah bentuk utama.[2] Cetirizine mempunyai selectivity 600 kali lipat atau lebih untuk reseptor H1 jika dibandingkan dengan lokasi lain, seperti muscarinic acetylcholine, serotonin, dopamine, dan α-adrenergic receptor.[2] Obat ini mempunyai selektivitas untuk reseptor H1 20.000 kali atau lebih jika dbandingkan dengan lima macam reseptor muscarinic acetylcholine, karenanya obat ini tidak mempunyai efek antikolinergis .[16][17] Obat ini menunjukan sifat inhibisi ringan pada kanal hERG (IC50 > 30 μM)[18] dan tidak menunjukkan efek kardiotoksisitas sampai dengan dosis 60 mg/hari, yaitu enam kali dosis yang direkomendasikan [2] dan dosis cetirizine tertinggi yang pernah dipelajari penggunaannya pada subjek yang sehat.[19]

Cetirizine hanya sedikit melintasi sawar darah otak, dan karenanya, hanya memberikan efek sedasi minimal jika dibandingkan dengan banyak macam antihistamin.[20] Suatu studi positron emission tomography (PET) menemukan bahwa reseptor H1 di otak ditempati sebanyak 12.6% untuk 10 mg cetirizine, 25.2% untuk 20 mg cetirizine, dan 67.6% untuk 30 mg hydroxyzine.[21] (Cetirizine dosis 10 mg memberikan efek antihistamin perifer yang setara dengan hydroxyzine 30 mg .)[22] Studi antihistamin menggunakan PET menunjukkan bahwa ikatan lebih dari 50% pada reseptor H1 di otak memberikan efek mengantuk dan penurunan kognitif yang lebih besar, sedangkan ikatan kurang dari 20% pada reseptor H1 di otak dianggap tidak menimbulkan efek sedasi.[23] In accordance, H1 receptor occupancy correlated well with subjective sleepiness for 30 mg hydroxyzine but there was no correlation for 10 or 20 mg cetirizine.[21] As such, brain penetration and brain H1 receptor occupancy by cetirizine are dose-dependent, and in accordance, while cetirizine at doses of 5 to 10 mg have been reported to be non-sedating or mildly sedating, a higher dose of 20 mg has been found to induce significant drowsiness in other studies.[21]

Cetirizine has been shown to inhibit eosinophil chemotaxis and LTB4 release.[24] At a dosage of 20 mg, Boone et al. found that it inhibited the expression of VCAM-1 in patients with atopic dermatitis.[24]

Pharmacokinetics

Absorption

Cetirizine is rapidly and extensively absorbed upon oral administration in tablet or syrup form.[2] The oral bioavailability of cetirizine is at least 70% and of levocetirizine is at least 85%.[1] The Tmax of cetirizine is approximately 1.0 hour regardless of formulation.[3] The pharmacokinetics of cetirizine have been found to increase linearly with dose across a range of 5 to 60 mg.[2] Its Cmax following a single dose has been found to be 257 ng/mL for 10 mg and 580 ng/mL for 20 mg.[3] Food has no effect on the bioavailability of cetirizine but has been found to delay the Tmax by 1.7 hours (i.e., to approximately 2.7 hours) and to decrease the Cmax by 23%.[2][3][25] Similar findings were reported for levocetirizine, which had its Tmax delayed by 1.25 hours and its Cmax decreased by about 36% when administered with a high-fat meal.[25] Steady-state levels of cetirizine occur within 3 days and there is no accumulation of the drug with chronic administration.[3] Following once-daily administration of 10 mg cetirizine for 10 days, the mean Cmax was 311 ng/mL.[26]

Distribution

The mean plasma protein binding of cetirizine has been found to be 93 to 96% across a range of 25 to 1,000 ng/mL independent of concentration.[3] Plasma protein binding of 88 to 96% has also been reported across multiple studies.[1] The drug is bound to albumin with high affinity, while α1-acid glycoprotein and lipoproteins contribute much less to total plasma protein binding.[1] The unbound or free fraction of levocetirizine has been reported to be 8%.[1] The true volume of distribution of cetirizine is unknown but is estimated to be 0.3 to 0.45 L/kg.[2][1] Cetirizine poorly and slowly crosses the blood–brain barrier, which is due mainly to its chemical properties but also to a minor extent to its activity as a P-glycoprotein substrate.[1]

Metabolism

Cetirizine does not undergo extensive metabolism.[2] It is notably not metabolized by the cytochrome P450 system.[27] Because of this, it does not interact significantly with drugs that inhibit or induce cytochrome P450 enzymes such as theophylline, erythromycin, clarithromycin, cimetidine, or alcohol.[2] While cetirizine does not undergo extensive metabolism or metabolism by the cytochrome P450 enzyme, it does undergo some metabolism by other means, the metabolic pathways of which include oxidation and conjugation.[2][3] Plasma radioactivity attributed to unchanged cetirizine is more than 90% at 2 hours, 80% at 10 hours, and 70% at 24 hours, indicating limited and slow metabolism.[3] The enzymes responsible for transformation of cetirizine have not been identified.[2]

Elimination

Cetirizine is eliminated approximately 70 to 85% in the urine and 10 to 13% in the feces.[2] About 50 or 60% of cetirizine eliminated in the urine is unchanged.[2][3] It is eliminated in the urine via an active transport mechanism.[3] The elimination half-life of cetirizine ranges from 6.5 to 10 hours in healthy adults, with a mean across studies of approximately 8.3 hours.[2][3] Its duration of action is at least 24 hours.[3] The elimination half-life of cetirizine is increased in the elderly (to 12 hours), in hepatic impairment (to 14 hours), and in renal impairment (to 20 hours).[3]

Chemistry

Cetirizine contains L- and D-stereoisomers. Chemically, levocetirizine is the active L-enantiomer of cetirizine. The drug is a member of the diphenylmethylpiperazine group of antihistamines. Analogues include cyclizine and hydroxyzine.

Synthesis

Cetirizine synthesis:[28]

The 1-(4-chlorophenylmethyl)-piperazine is alkylated with methyl (2-chloroethoxy)-acetate in the presence of sodium carbonate and xylene solvent to produce the Sn2 substitution product in 28% yield. Saponification of the acetate ester is done by refluxing with potassium hydroxide in absolute ethanol to afford a 56% yield of the potassium salt intermediate. This is then hydrolyzed with aqueous HCl and extracted to give an 81% yield of the carboxylic acid product.

Society and culture

A package of 10 mg cetirizine tablets.
Zyrtec-D, a combination of cetirizine and pseudoephedrine.

Brand names

Cetirizine is marketed under the brand names Alatrol, Alerid, Alzene, Cetirin, Cetzine, Cezin, Cetgel, Cirrus, Histazine, Humex, Letizen, Okacet (Cipla), Reactine, Razene, Rigix, Sensahist (Oethmann, South Africa), Triz, Zetop, Zirtec, Zirtek, Zodac, Zyllergy, Zynor, Zyrlek, and Zyrtec (Johnson & Johnson), among others.

Availability

Formerly prescription-only in many countries, cetirizine is now available without prescription in most countries. In some countries it is available over-the-counter only in packages containing seven or ten 10 mg doses.

Like many other antihistamine medications, cetirizine is commonly prescribed in combination with pseudoephedrine, a decongestant. These combinations are often marketed using the same brand name as the cetirizine with a "-D" suffix (Zyrtec-D, Virlix-D, etc.)

References

  1. ^ a b c d e f g h Chen C (2008). "Physicochemical, pharmacological and pharmacokinetic properties of the zwitterionic antihistamines cetirizine and levocetirizine". Curr. Med. Chem. 15 (21): 2173–91. doi:10.2174/092986708785747625. PMID 18781943. 
  2. ^ a b c d e f g h i j k l m n o p q r s t Portnoy JM, Dinakar C (2004). "Review of cetirizine hydrochloride for the treatment of allergic disorders". Expert Opin Pharmacother. 5 (1): 125–35. doi:10.1517/14656566.5.1.125. PMID 14680442. 
  3. ^ a b c d e f g h i j k l m n Simons FE, Simons KJ (1999). "Clinical pharmacology of new histamine H1 receptor antagonists". Clin Pharmacokinet. 36 (5): 329–52. doi:10.2165/00003088-199936050-00003. PMID 10384858. 
  4. ^ Simons FE (2002). "Comparative pharmacology of H1 antihistamines: clinical relevance". Am. J. Med. 113 Suppl 9A (9): 38S–46S. doi:10.1016/s0002-9343(02)01436-5. PMID 12517581. 
  5. ^ a b c d e British national formulary : BNF 76 (edisi ke-76). Pharmaceutical Press. 2018. hlm. 279. ISBN 9780857113382. 
  6. ^ a b c d e "Cetirizine Hydrochloride Monograph for Professionals". Drugs.com (dalam bahasa Inggris). American Society of Health-System Pharmacists. Diakses tanggal 3 March 2019. 
  7. ^ "Cetirizine Pregnancy and Breastfeeding Warnings". Drugs.com (dalam bahasa Inggris). Diakses tanggal 3 March 2019. 
  8. ^ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery (dalam bahasa Inggris). John Wiley & Sons. hlm. 549. ISBN 9783527607495. 
  9. ^ "NADAC as of 2019-02-27". Centers for Medicare and Medicaid Services (dalam bahasa Inggris). Diakses tanggal 3 March 2019. 
  10. ^ "The Top 300 of 2020". ClinCalc. Diakses tanggal 11 April 2020. 
  11. ^ "Cetirizine - Drug Usage Statistics". ClinCalc. Diakses tanggal 11 April 2020. 
  12. ^ "Zyrtec Side Effects". drugs.com. Drugs.com. Diakses tanggal 21 August 2015. 
  13. ^ Ekhart, C.; Van Der Horst, P.; Van Hunsel, F. (2016). "Unbearable Pruritus After Withdrawal of (Levo)cetirizine". Drug Safety - Case Reports. 3 (1): 16. doi:10.1007/s40800-016-0041-9. PMC 5124431 alt=Dapat diakses gratis. PMID 27889900. 
  14. ^ "Cetirizine (Zyrtec) Withdrawal & Unbearable Itching". People's Pharmacy. Diakses tanggal 9 September 2017. 
  15. ^ "addicted to zyrtec?". MedHelp. Diakses tanggal 9 September 2017. 
  16. ^ Zhang L, Cheng L, Hong J (2013). "The clinical use of cetirizine in the treatment of allergic rhinitis". Pharmacology. 92 (1–2): 14–25. doi:10.1159/000351843. PMID 23867423. 
  17. ^ Orzechowski RF, Currie DS, Valancius CA (2005). "Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models". Eur. J. Pharmacol. 506 (3): 257–64. doi:10.1016/j.ejphar.2004.11.006. PMID 15627436. 
  18. ^ Taglialatela M, Pannaccione A, Castaldo P, Giorgio G, Zhou Z, January CT, Genovese A, Marone G, Annunziato L (1998). "Molecular basis for the lack of HERG K+ channel block-related cardiotoxicity by the H1 receptor blocker cetirizine compared with other second-generation antihistamines". Mol. Pharmacol. 54 (1): 113–21. doi:10.1124/mol.54.1.113. PMID 9658196. 
  19. ^ Hulhoven R, Rosillon D, Letiexhe M, Meeus MA, Daoust A, Stockis A (2007). "Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study". Eur. J. Clin. Pharmacol. 63 (11): 1011–7. doi:10.1007/s00228-007-0366-5. PMID 17891537. The equivalent dose of 60 mg cetirizine is also the highest dose ever administered in healthy subjects [13]. 
  20. ^ Gupta, A; Chatelain P; Massingham R; Jonsson EN; Hammarlund-Udenaes M (February 2006). "Brain distribution of cetirizine enantiomers: comparison of three different tissue-to-plasma partition coefficients: K(p), K(p,u), and K(p,uu)". Drug Metab. Dispos. 34 (2): 318–23. doi:10.1124/dmd.105.007211. PMID 16303872. 
  21. ^ a b c Tashiro M, Kato M, Miyake M, Watanuki S, Funaki Y, Ishikawa Y, Iwata R, Yanai K (2009). "Dose dependency of brain histamine H(1) receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin". Hum Psychopharmacol. 24 (7): 540–8. doi:10.1002/hup.1051. PMID 19697300. 
  22. ^ van den Elzen MT, van Os-Medendorp H, van den Brink I, van den Hurk K, Kouznetsova OI, Lokin AS, Laheij-de Boer AM, Röckmann H, Bruijnzeel-Koomen CA, Knulst AC (2017). "Effectiveness and safety of antihistamines up to fourfold or higher in treatment of chronic spontaneous urticaria". Clin Transl Allergy. 7: 4. doi:10.1186/s13601-017-0141-3. PMC 5309999 alt=Dapat diakses gratis. PMID 28289538. [...] 30 mg of hydroxyzine equals about 10 mg cetirizine [11] [...] 
  23. ^ Yanai K, Tashiro M (2007). "The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies". Pharmacol. Ther. 113 (1): 1–15. doi:10.1016/j.pharmthera.2006.06.008. PMID 16890992. 
  24. ^ a b Boone M, Lespagnard L, Renard N, Song M, Rihoux JP (July 2000). "Adhesion molecule profiles in atopic dermatitis vs. allergic contact dermatitis: pharmacological modulation by cetirizine". J Eur Acad Dermatol Venereol. 14 (4): 263–6. doi:10.1046/j.1468-3083.2000.00017.x. PMID 11204513. Diarsipkan dari versi asli tanggal 5 January 2013. Diakses tanggal 19 November 2009. 
  25. ^ a b Paśko P, Rodacki T, Domagała-Rodacka R, Palimonka K, Marcinkowska M, Owczarek D (2017). "Second generation H1 – antihistamines interaction with food and alcohol-A systematic review". Biomed. Pharmacother. 93: 27–39. doi:10.1016/j.biopha.2017.06.008. PMID 28622592. 
  26. ^ "Zyrtec prescribing information" (PDF). May 2006. Diarsipkan dari versi asli (PDF) tanggal 4 January 2010. Diakses tanggal 19 November 2009. 
  27. ^ Massoud Mahmoudi (2 June 2016). Allergy and Asthma: Practical Diagnosis and Management. Springer. hlm. 574–. ISBN 978-3-319-30835-7. 
  28. ^ US patent 4525358, Baltes E, De Lannoy J, Rodriguez L, "2-[4-(Diphenylmethyl)-1-piperazinyl]-acetic acids and their amides", dikeluarkan tanggal 25 June 1985, diberikan kepada UCB Pharmaceuticals, Inc. 
  • "Cetirizine". Drug Information Portal. U.S. National Library of Medicine. 

Templat:Antihistamines Templat:Histamine receptor modulators Templat:PAF receptor modulators

Diperoleh dari "https://wiki-indonesia.club/w/index.php?title=Setirizin&oldid=17060154"