PMID- 31674861
OWN - NLM
STAT- MEDLINE
DCOM- 20200909
LR  - 20221207
IS  - 1557-7732 (Electronic)
IS  - 1080-7683 (Print)
IS  - 1080-7683 (Linking)
VI  - 35
IP  - 10
DP  - 2019 Dec
TI  - Pharmacokinetics, Safety, and Intraocular Pressure-Lowering Profile of Omidenepag 
      Isopropyl, a Selective, Nonprostaglandin, Prostanoid EP2 Receptor Agonist, in 
      Healthy Japanese and Caucasian Volunteers (Phase I Study).
PG  - 542-550
LID - 10.1089/jop.2019.0044 [doi]
AB  - Purpose: Omidenepag isopropyl (OMDI) is a prodrug of OMD, a selective, 
      nonprostaglandin, prostanoid EP2 receptor agonist. This phase I study aimed to 
      investigate the pharmacokinetic properties, safety, and intraocular pressure 
      (IOP)-lowering efficacy of OMDI. Methods: Fourteen healthy male volunteers (7 
      Japanese and 7 Caucasian) 20-35 years of age received 1 drop of OMDI 0.0025% at 
      9:00 h in both eyes for 7 days. Blood samples were taken predose and up to 8 h 
      postdose on days 1, 3, and 7. The plasma concentration of OMD was determined 
      using high-performance liquid chromatography-tandem mass spectrometry. 
      Pharmacokinetic parameters measured included the maximum plasma concentration 
      (C(max)) and the half-life (t((1/2))) of OMD. IOP, adverse events (AEs), ophthalmic 
      examinations, vital signs, and laboratory values were assessed. Results:C(max) 
      for all subjects was reached after 10-15 min and decreased with a t((1/2)) of 
       approximately 30 min. Ad hoc statistical analyses found significant differences in some 
      pharmacokinetic parameters between Japanese and Caucasian subjects, likely due to 
      differences in body weight. These differences reduced over 7 days of dosing and 
      were not thought to be clinically meaningful. There was no OMD accumulation after 
      7 days of repeated dosing. Mean IOP was reduced by  approximately 4-5 mmHg between baseline and 
      2 h postdose, remaining stable from day 3 onward. All AEs were mild and 
      considered treatment related. Conclusions: Pharmacokinetic parameters of OMD were 
      similar between Japanese and Caucasian subjects. There was no accumulation of OMD 
      after 7 days of dosing. OMDI was well tolerated and demonstrated clinically 
      significant IOP reductions.
FAU - Aihara, Makoto
AU  - Aihara M
AD  - Department of Ophthalmology, University of Tokyo, Bunkyo-ku, Japan.
FAU - Lu, Fenghe
AU  - Lu F
AD  - Santen, Inc., Emeryville, California.
FAU - Kawata, Hisashi
AU  - Kawata H
AD  - Santen Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Tanaka, Yuki
AU  - Tanaka Y
AD  - Santen Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Yamamura, Kenzo
AU  - Yamamura K
AD  - Santen Pharmaceutical Co., Ltd., Ikoma, Japan.
FAU - Odani-Kawabata, Noriko
AU  - Odani-Kawabata N
AD  - Santen, Inc., Emeryville, California.
AD  - Santen Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Shams, Naveed K
AU  - Shams NK
AD  - Santen, Inc., Emeryville, California.
AD  - Santen Pharmaceutical Co., Ltd., Osaka, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20191101
PL  - United States
TA  - J Ocul Pharmacol Ther
JT  - Journal of ocular pharmacology and therapeutics : the official journal of the 
      Association for Ocular Pharmacology and Therapeutics
JID - 9511091
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - G0G0H52U6K (omidenepag isopropyl)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Adult
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Glycine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Healthy Volunteers
MH  - Humans
MH  - Intraocular Pressure/*drug effects
MH  - Japan
MH  - Male
MH  - Ophthalmic Solutions/administration & dosage/adverse effects/*pharmacokinetics
MH  - Pyrazoles/administration & dosage/adverse effects/*pharmacokinetics
MH  - Pyridines/administration & dosage/adverse effects/*pharmacokinetics
MH  - Receptors, Prostaglandin E, EP2 Subtype/*agonists
MH  - White People
MH  - Young Adult
PMC - PMC6918846
OTO - NOTNLM
OT  - EP2 receptor agonist
OT  - glaucoma
OT  - intraocular pressure
OT  - omidenepag isopropyl
OT  - pharmacokinetics
OT  - phase I
COIS- M.A. has received research support and honoraria/consultation fees from Santen 
      and has participated in a company-sponsored speaker's bureau for Santen. The 
      following authors are all employees of Santen: Fenghe Lu, Hisashi Kawata, Yuki 
      Tanaka, Kenzo Yamamura, Noriko Odani-Kawabata, and Naveed K. Shams.
EDAT- 2019/11/02 06:00
MHDA- 2020/09/10 06:00
PMCR- 2019/12/06
CRDT- 2019/11/02 06:00
PHST- 2019/11/02 06:00 [pubmed]
PHST- 2020/09/10 06:00 [medline]
PHST- 2019/11/02 06:00 [entrez]
PHST- 2019/12/06 00:00 [pmc-release]
AID - 10.1089/jop.2019.0044 [pii]
AID - 10.1089/jop.2019.0044 [doi]
PST - ppublish
SO  - J Ocul Pharmacol Ther. 2019 Dec;35(10):542-550. doi: 10.1089/jop.2019.0044. Epub 
      2019 Nov 1.