title: Pharmacodynamics, pharmacokinetics, and safety of AM211: a novel and potent antagonist of the prostaglandin D2 receptor type 2.
abstract: The prostaglandin D(2) receptor type 2 (DP2) and its ligand, PGD(2), have been implicated in the development of asthma and other inflammatory diseases. The authors evaluated the pharmacodynamics, pharmacokinetics and safety of [2'-(3-benzyl-1-ethyl-ureidomethyl)-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl]-acetic acid sodium salt (AM211), a novel and potent DP2 antagonist, in healthy participants. Single and multiple doses of AM211 demonstrated dose-dependent inhibition of eosinophil shape change in blood with near-complete inhibition observed at trough after dosing 200 mg once daily for 7 days. Maximum plasma concentrations and exposures of AM211 increased in a greater-than-dose-proportional manner after single and multiple dosing. After multiple dosing, the exposures on day 7 were higher than on day 1 with accumulation ratio values ranging from 1.4 to 1.5. Mean terminal half-life values ranged from 14 to 25 hours across the dose range of 100 to 600 mg. AM211 was well tolerated at all doses in both the single- and multiple-dose cohorts. These data support additional clinical studies to evaluate AM211 in asthma and other inflammatory diseases.
authors: Amira Pharmaceuticals, San Diego, CA, USA. gretchen.bain@amirapharm.com
authors: G
authors: G
authors: Bain
authors: C D
authors: CD
authors: King
authors: J
authors: J
authors: Brittain
authors: J P
authors: JP
authors: Hartung
authors: I
authors: I
authors: Dearmond
authors: B
authors: B
authors: Stearns
authors: Y P
authors: YP
authors: Truong
authors: J H
authors: JH
authors: Hutchinson
authors: J F
authors: JF
authors: Evans
authors: K
authors: K
authors: Holme
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D004311:Double-Blind Method; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008782:Methylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008875:Middle Aged; D010648:Phenylacetates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015230:Prostaglandin D2 / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055815:Young Adult
chemical_list: C560624:(2'-(3-benzyl-1-ethylureidomethyl)-6-methoxy-4'-trifluoromethylbiphenyl-3-yl)acetic acid; D008782:Methylurea Compounds; D010648:Phenylacetates; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor