title: Design, synthesis, bioconversion, and pharmacokinetics evaluation of new ester prodrugs of olmesartan.
abstract: Synthesis of new ester prodrugs of olmesartan is described. Their in vitro stabilities in simulated gastric juice, rat plasma, and rat liver microsomes were tested. And the pharmacokinetic parameters for olmesartan after their oral administration were also estimated and compared with those in case of olmesartan medoxomil. Compounds 13 and 14 demonstrated high stability in simulated gastric juice and were rapidly metabolized to olmesartan in rat liver microsomes and rat plasma in vitro. In addition, C(max) and AUC(last) parameters were significantly increased in case of compounds 13 and 14 compared with olmesartan medoxomil. These results indicate that compounds 13 and 14 with cyclohexylcarboxyethyl and adamantylcarboxymethyl promoieties, respectively, are promising prodrugs of olmesartan with markedly increased oral bioavailability.
authors.affiliation: College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Jeong-Soo
authors.initials: JS
authors.lastname: Chang
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: El-Gamal
authors.forename: Woong San
authors.initials: WS
authors.lastname: Lee
authors.forename: Hanan S
authors.initials: HS
authors.lastname: Anbar
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Chung
authors.forename: Hyun-Il
authors.initials: HI
authors.lastname: Kim
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Cho
authors.forename: Bong Sang
authors.initials: BS
authors.lastname: Lee
authors.forename: Sun Ahe
authors.initials: SA
authors.lastname: Lee
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Moon
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Lee
authors.forename: Hong-Ryeol
authors.initials: HR
authors.lastname: Jeon
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Oh
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004952:Esters; D005750:Gastric Juice / Q000378:metabolism; D006207:Half-Life; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004952:Esters; D007093:Imidazoles; D011355:Prodrugs; D013777:Tetrazoles; C437965:olmesartan