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Maropitant
Clinical data
Pronunciation/məˈrɒpɪtænt/ mə-ROP-i-tant
Trade namesCerenia
Other namesCJ-11,972
AHFS/Drugs.comFDA Professional Drug Information
License data
SQ, IV
Drug classAntiemetic
ATCvet code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityOral: 20–30% dogs, 50% cats
SQ: 90% (both)
Protein binding99.5%
MetabolismLiver (CYP3A12 and CYP2D15)
MetabolitesCJ-18,518
Elimination half-life6–8 hours (SQ)
Duration of action24 hours (SQ)
Identifiers
  • 2S,3S)-N-(5-tert-Butyl-2-methoxybenzyl)-2-(diphenylmethyl)-1-azabicyclo[2.2.2]octan-3-amine
JSmol)
  • CC(C)(C)C1=CC(=C(C=C1)OC)CNC2C3CCN(C2C(C4=CC=CC=C4)C5=CC=CC=C5)CC3
  • InChI=1S/C32H40N2O.C6H8O7.H2O/c1-32(2,3)27-15-16-28(35-4)26(21-27)22-33-30-25-17-19-34(20-18-25)31(30)29(23-11-7-5-8-12-23)24-13-9-6-10-14-24;7-3(8)1-6(13,5(11)12)2-4(9)10;/h5-16,21,25,29-31,33H,17-20,22H2,1-4H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);1H2/t30-,31-;;/m0../s1
  • Key:PGVSXRHFXJOMGW-YBZGWEFGSA-N

Maropitant, sold as maropitant citrate under the brand name Cerenia by Zoetis, is a anti-nausea medication used in dogs and cats. Both the tablet and injectable versions were approved by the

anti-anxiety, and anti-inflammatory
effects. One of the most common side effects is pain when administered subcutaneously.

Medical uses

Injectable maropitant is used in

cats.[1][3][4][5][6]

Maropitant is effective in treating vomiting from a variety of causes, including

renal failure;[7][8] when given beforehand, it can prevent vomiting caused by using an opioid as a premedication.[5][9] Some have claimed that maropitant is better at treating vomiting than nausea, pointing to cats with chronic kidney disease who, when receiving maropitant, had a reduction in vomiting but no corresponding increase in appetite.[2]

Maropitant has also been used in cases of acute episodes of rapid or labored breathing to prevent vomiting that could lead to aspiration pneumonia.[10] It has also been given in combination with a benzodiazepine to cats prior to stressful events (such as a vet visit) to possibly relieve hypersensitivity.[11]

When compared to other anti-emetics, maropitant has similar or greater effectiveness to

vomiting center in brain) induced by apomorphine or xylazine.[6] It works better than chlorpromazine and metoclopramide for peripheral-induced vomiting (caused by actions in the gastrointestinal tract) induced by syrup of ipecac.[12] Unlike dimenhydrinate and acepromazine, which are used for motion sickness, maropitant does not cause sedation.[13]

Maropitant has weak anti-inflammatory effects, and has thus been used as an adjunct treatment in severe

guinea pigs to relieve pain caused by ileus (impaired bowel movements), though it lacks antiemetic effects in rabbits, who cannot vomit.[15]

Maropitant is given

intravenously; while intravenous administration is an indicated use in Europe, it is off-label in the U.S.[5][7]

Contraindications

Maropitant is only indicated for dogs at least 16 weeks old, as some very young puppies suffered bone marrow hypoplasia (incomplete development ).[3] It should also not be used in animals with suspected GI obstruction or toxin ingestion.[8][13]

It is not recommended to give maropitant for more than five consecutive days, as it tends to accumulate in the body due to one of the liver enzymes responsible for its metabolism,

beagles who were given maropitant for two weeks in a row showed no signs of toxicity.[13]

Because maropitant is metabolized by the liver, caution should be taken when giving it to dogs with

potassium channels.[17]

Side effects

Maropitant is safer than other antiemeticsused in veterinary medicine, in part because of its high specificity for its target and thus not binding to other receptors in the

loss of appetite, and vomiting.[7][11] Eight percent of dogs taking maropitant at doses meant to prevent motion sickness vomited right after, likely due to the local effects maropitant had on the gastrointestinal tract. Small amounts of food beforehand can prevent such post-administration vomiting.[6]

One of the most common side effects of subcutaneous administration is moderate to severe pain at the injection site.

beta-cyclodextrin to increase solubility; at cooler temperatures, more of the maropitant remains bound to the cyclodextrin, leaving less maropitant unbound.[9][15]

While there is no pain related to the intravenous administration of maropitant, pushing a dose in too quickly can temporarily reduce blood pressure.[5][13]

Fewer than 1 in 10,000 dogs and cats experience

anaphylactic reactions.[17]

Overdose

Signs of maropitant overdose include

salivation and nasal discharge, while overdose of intravenous maropitant can sometimes lead to reddish urine.[7] The LD50 is high, being over 2,000 mg/kg for oral maropitant in rats.[18]

Green package and dark brown vial
Packaging of injectable maropitant (Cerenia), as sold by Zoasis

Pharmacology

Mechanism of action

Vomiting is caused when impulses from the

vomiting center in the medulla. Motion sickness specifically occurs when signals to the CRTZ originate from the inner ear: motion is sensed by the fluid of the semicircular canals, which causes overstimulation. The signal travels to the brain's vestibular nuclei, then to the CRTZ, and finally to the vomiting center.[19]

Maropitant has a similar structure to

neurokinin 1 (NK1)[3][20]. It is highly selective for NK1 over NK2 and NK3.[5][15] Maropitant binds to the neurokinin receptors in the vagus nerves leaving the GI tract, as well as to receptors in the CRTZ and the vomiting center.[12][19] By virtue of working at the last step in triggering vomiting, it can prevent a broader range of stimuli than most antiemetics can.[20] It is effective against emetogens that act at the central nervous system (such as apomorphine in dogs and xylazine in cats), those that act in the periphery (e.g. syrup of ipecac),[9][13] and those that act in both (e.g. cisplatin).[6]

4 boxes
Packaging of oral maropitant

Pharmacokinetics

Maropitant's bioavailability is unaffected by the presence of food.[7] Bioavailability is 91% at the standard subcutaneous dose but 24% at the standard oral dose; the standard oral dose is higher to partially compensate for incomplete bioavailability.[3][13] It binds to plasma proteins at a rate of 99.5%; it has a low volume of distribution (9 L/kg) and is thus not extensively absorbed.[3][5] Subcutaneously administered maropitant had peak plasma concentration around half an hour after administration; the mean half-life is 6–8 hours, and a single dose lasts 24 hours in dogs.[5] Orally administered maropitant reached its peak plasma concentration within two hours.[7]

Maropitant undergoes

CYP2D15 (which has high affinity for maropitant and clears over 90% of it) but also by the lower-affinity CYP3A12.[6][7] Repeat dosing of maropitant eventually saturates CYP2D15, causing the drug to accumulate due to reduced clearance.[3] Thus, it is recommended to not use maropitant for more than five days straight, and to have a two-day rest period to allow maropitant to clear the body to prevent accumulation.[13][21] Maropitant has over 21 metabolites, though its major one (produced by hydroxylation) is CJ-18,518.[7]

Maropitant clearance is slower in cats.[13]

References

  1. ^ a b "FDA Approves First Drug To Prevent and Treat Vomiting in Dogs". US Food & Drug Administration. 28 February 2007. Archived from the original on 2016-10-24. Retrieved 18 May 2018.
  2. ^
    ISBN 978-1-118-85588-1
    .
  3. ^ a b c d e f g h "Cerenia". Drugs.com. Retrieved 27 March 2018.
  4. ^ "Cerenia Injectable Solution for Animal Use". Drugs.com. 29 March 2018. Retrieved 2 May 2018.
  5. ^ a b c d e f g h CVMP assessment report for Cerenia new route of administration (intravenous use) for the solution for injection (PDF) (Report). European Medicines Agency. 10 April 2015.
  6. ^
    ISBN 978-0-7020-2858-8
    .
  7. ^
    ISBN 978-0-470-95964-0
    .
  8. ^
    ISBN 978-0-323-06876-5
    .
  9. ^
    ISBN 978-1-118-52620-0
    .
  10. ^ a b Tamborini, Alice (November 2016). "Maropitant & Canine Chronic Bronchitis" (PDF). Clinician's Brief. Retrieved 29 March 2018.
  11. ^
    ISBN 978-1-4557-7402-9
    .
  12. ^
    ISBN 978-1-4377-0282-8
    .
  13. ^ a b c d e f g h Trepanier, Lauren A. (February 2015). "Maropitant: Novel Antiemetic" (PDF). Clinician's Brief. Retrieved 28 March 2018.
  14. PMID 28844293
    .
  15. ^
    ISSN 1557-5063
    .
  16. OCLC 903234097
    .
  17. ^ a b "Contra-indications, warnings, etc". NOAH Compendium. National Office of Animal Health. Retrieved 11 May 2018.
  18. ^ Bahri, Lotfi. "Maropitant: A novel treatment for acute vomiting in dogs". dvm360.com. Retrieved 28 March 2018.
  19. ^ a b Graham, Heather (June 2013). "Motion Sickness in Small Animals: Pathophysiology & Treatment". Clinician's Brief. Retrieved 29 March 2018.
  20. ^ a b Bahri, Lotfi (1 September 2009). "Maropitant's pharmacokinetics and pharmacology". dvm360. Retrieved 2 May 2018.
  21. ISBN 978-0-323-24300-1
    .

External links
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