Discovery of olmesartan hexetil: a new potential prodrug of olmesartan.
Synthesis of a new ester prodrug of olmesartan, olmesartan hexetil (1), is described. It is in vitro stabilities and in vivo pharmacokinetics (PK) were evaluated. It showed high stability in simulated gastric juice, and was rapidly hydrolyzed to olmesartan in rat liver microsomes and rat plasma in vitro. C(max) and AUC(last) for olmesartan were significantly increased in case of hexetil prodrug, compared with olmesartan medoxomil. Olmesartan hexetil is proposed to be an efficient prodrug of olmesartan with markedly increased oral bioavailability.
Biomedical Research Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Mohammed I
MI
El-Gamal
Hanan S
HS
Anbar
Hye Jin
HJ
Chung
Hyun-Il
HI
Kim
Young-Jin
YJ
Cho
Bong Sang
BS
Lee
Sun Ahe
SA
Lee
Ji Yun
JY
Moon
Dong Jin
DJ
Lee
Dow
D
Kwon
Won-Jai
WJ
Choi
Hong-Ryeol
HR
Jeon
Chang-Hyun
CH
Oh
D047228:Angiotensin II Type 1 Receptor Blockers / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D055808:Drug Discovery; D004355:Drug Stability; D004952:Esters / Q000138:chemical synthesis; D005750:Gastric Juice / Q000737:chemistry / Q000378:metabolism; D007093:Imidazoles / Q000097:blood / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000097:blood / Q000138:chemical synthesis* / Q000493:pharmacokinetics*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D004952:Esters; D007093:Imidazoles; D011355:Prodrugs; D013777:Tetrazoles; C437965:olmesartan