ORIGINAL ARTICLE  

Syntheses and Pharmacokinetic Studies of Prodrug Esters for the Development of Oral Carbapenem, L-084

Takeshi Isoda, Hideki Ushirogochi, Koichi Satoh, Tsuyoshi Takasaki, Itsuki Yamamura, Chisato Sato, Ado Mihira, Takao Abe, Satoshi Tamai, Shigeki Yamamoto, Toshio Kumagai, Yoshimitsu Nagao

Received: February 16, 2006 / Accepted: April 13, 2006
© Japan Antibiotics Research Association

Abstract We discovered an orally active carbapenem, L-084, through pharmacokinetic studies on various prodrug esters of (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[1-(1,3-thiazolin-2-yl)azetidin-3-yl]thio-1-carbapen-2-em-3-carboxylic acid (LJC11,036). L-084 showed a strong antimicrobial activity against Gram-positive and Gram-negative bacteria and exhibited the highest intestinal absorption among synthesized prodrugs of LJC11,036.

Keywords 1β-methylcarbapenem, prodrug ester, azetidine, oral administration, pharmacokinetics


T. Isoda (Corresponding author), H. Ushirogochi, K. Satoh, T. Takasaki, I. Yamamura, C. Sato, A. Mihira, T. Abe, S. Tamai, S. Yamamoto, T. Kumagai: Medical Research Laboratories, Wyeth K.K., 1-6-34 Kashiwa-cho, Shiki-shi, Saitama 353-8511, Japan, E-mail: isoda@konicaminolta.jp
Y. Nagao: Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima-shi, Tokushima 770-8505, Japan