Editing Loratadine (section)

== Pharmacology ==
=== Pharmacodynamics ===
Loratadine is a [[tricyclic antihistamine]], which acts as a selective [[inverse agonist]] of peripheral [[histamine]] [[histamine H1 receptor|H<sub>1</sub> receptors]].<ref name="Mutschler" /><ref name=Devillier2008rev>{{cite journal | vauthors = Devillier P, Roche N, Faisy C | title = Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine, and levocetirizine: a comparative review | journal = Clinical Pharmacokinetics | volume = 47 | issue = 4 | pages = 217–30 | year = 2008 | pmid = 18336052 | doi = 10.2165/00003088-200847040-00001 | s2cid = 9189476 }}</ref> The potency of second generation histamine antagonists is (from strongest to weakest) [[desloratadine]] ([[Dissociation constant|K<sub>i</sub>]] 0.4&nbsp;nM) > [[levocetirizine]] (K<sub>i</sub> 3&nbsp;nM) > [[cetirizine]] (K<sub>i</sub> 6&nbsp;nM) > [[fexofenadine]] (K<sub>i</sub> 10&nbsp;nM) > terfenadine > loratadine.  However, the onset of action varies significantly and clinical efficacy is not always directly related to only the H<sub>1</sub> receptor potency, as the concentration of free drug at the receptor must also be considered.<ref>{{cite journal | vauthors = Church MK, Church DS | title = Pharmacology of antihistamines | journal = Indian Journal of Dermatology | volume = 58 | issue = 3 | pages = 219–24 | date = May 2013 | pmid = 23723474 | pmc = 3667286 | doi = 10.4103/0019-5154.110832 | doi-access = free }}</ref><ref name=Devillier2008rev/> Loratadine also shows anti-inflammatory properties independent of H<sub>1</sub> receptors.<ref name="pmid15631542">{{cite journal | vauthors = Bielory L, Lien KW, Bigelsen S | title = Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis | journal = Drugs | volume = 65 | issue = 2 | pages = 215–28 | date = 2005 | pmid = 15631542 | doi = 10.2165/00003495-200565020-00004 | s2cid = 46791611 | url = }}</ref><ref name="pmid23268457">{{cite journal | vauthors = Canonica GW, Blaiss M | title = Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence | journal = The World Allergy Organization Journal | volume = 4 | issue = 2 | pages = 47–53 | date = February 2011 | pmid = 23268457 | pmc = 3500039 | doi = 10.1097/WOX.0b013e3182093e19 | url = }}</ref> The effect is exhibited through suppression of the [[NF-κB]] pathway, and by regulating the release of cytokines and chemokines, thereby regulating the recruitment of inflammatory cells.<ref name="pmid32251678">{{cite journal | vauthors = Hunto ST, Kim HG, Baek KS, Jeong D, Kim E, Kim JH, Cho JY | title = Loratadine, an antihistamine drug, exhibits anti-inflammatory activity through suppression of the NF-kB pathway | journal = Biochemical Pharmacology | volume = 177 | issue = | pages = 113949 | date = July 2020 | pmid = 32251678 | doi = 10.1016/j.bcp.2020.113949| s2cid = 215408324 }}</ref><ref name="pmid15245363">{{cite journal | vauthors = Fumagalli F, Baiardini I, Pasquali M, Compalati E, Guerra L, Massacane P, Canonica GW | title = Antihistamines: do they work? Further well-controlled trials involving larger samples are needed | journal = Allergy | volume = 59 | issue = Suppl 78 | pages = 74–7 | date = August 2004 | pmid = 15245363 | doi = 10.1111/j.1398-9995.2004.00573.x| s2cid = 39936983 }}</ref>

=== Pharmacokinetics ===
Loratadine is given orally, is well absorbed from the gastrointestinal tract, and has rapid [[first-pass metabolism|first-pass hepatic metabolism]]; it is metabolized by [[isoenzyme]]s of the [[cytochrome P450]] system, including [[CYP3A4]], [[CYP2D6]], and, to a lesser extent, several others.<ref name=Foye>{{cite book | vauthors = Nelson WL | veditors = Williams DH, Foye WO, Lemke TL |title=Foye's principles of medicinal chemistry |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2002 |chapter=Antihistamines and related antiallergic and antiulcer agents |pages=805 |isbn=978-0-683-30737-5}}</ref><ref>{{cite journal | vauthors = Ghosal A, Gupta S, Ramanathan R, Yuan Y, Lu X, Su AD, Alvarez N, Zbaida S, Chowdhury SK, Alton KB | title = Metabolism of loratadine and further characterization of its in vitro metabolites | journal = Drug Metabolism Letters | volume = 3 | issue = 3 | pages = 162–70 | date = August 2009 | pmid = 19702548 | doi = 10.2174/187231209789352067 }}</ref> Loratadine is almost totally (97–99%) bound to [[plasma proteins]]. Its metabolite [[desloratadine]], which is largely responsible for the antihistaminergic effects, binds to plasma proteins by 73–76%.<ref name="Austria-Codex" />

Loratadine's peak effect occurs after 1–2 hours, and its biological [[half life]] is on average eight hours (range 3 to 20 hours) with [[desloratadine]]'s half-life being 27 hours (range 9 to 92 hours), accounting for its long-lasting effect.<ref>{{cite journal | vauthors = Affrime M, Gupta S, Banfield C, Cohen A | title = A pharmacokinetic profile of desloratadine in healthy adults, including elderly | journal = Clinical Pharmacokinetics | volume = 41 | issue = Suppl 1 | pages = 13–9 | year = 2002 | pmid = 12169042 | doi = 10.2165/00003088-200241001-00003 | s2cid = 25555379 }}</ref> About 40% is excreted as [[Biotransformation#Phase II reaction|conjugated metabolites]] into the urine, and a similar amount is excreted into the feces. Traces of unmetabolised loratadine can be found in the urine.<ref name="Austria-Codex" />

In structure, it is closely related to [[tricyclic antidepressant]]s, such as [[imipramine]], and is distantly related to the atypical [[antipsychotic]] [[quetiapine]].<ref name="pmid10444229">{{cite journal | vauthors = Kay GG, Harris AG | title = Loratadine: a non-sedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation | journal = Clinical and Experimental Allergy | volume = 29 | issue = Suppl 3 | pages = 147–50 | date = July 1999 | pmid = 10444229 | doi = 10.1046/j.1365-2222.1999.0290s3147.x | s2cid = 26012715 }}</ref>