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Biapenem, Ritipenem, Panipenem, and Sulopenem
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Sulopenem is a parenteral penem that demonstrates high activity against Gram-positive, Gram-negative, and anaerobic bacteria (Gootz et al., 1989; Yoshida et al., 1996; Hamilton-Miller, 2003). Because it is stable in relation to renal DHP-1, it does not require concomitant administration of an inhibitor of this enzyme (Gootz et al., 1990). The chemical structure of sulopenem is shown in Figure 42.4. Oral prodrugs of sulopenem were developed by Pfizer but phase II clinical studies were abandoned in 2010.
Tebipenem, the first oral carbapenem antibiotic
Published in Expert Review of Anti-infective Therapy, 2018
Akash Jain, Luke Utley, Thomas R. Parr, Thomas Zabawa, Michael J. Pucci
No oral carbapenems are currently marketed for use in adult patients. Two oral penems, faropenem and sulopenem (Figure 1, compounds 6 and 7), reached advanced stages of clinical development, but neither has gained FDA approval to date [15]. Faropenem [16] is marketed in Japan by Daiichi Sankyo, but after FDA review, it was determined in 2006 that more clinical data would be necessary for US approval and there is no indication that those studies are ongoing or planned. Sulopenem is currently being developed by Iterum Therapeutics. Phase 2 clinical studies of sulopenem are complete and it is reportedly undergoing formulation development to improve prior oral pharmacokinetic challenges [17]. The lead prodrug of sulopenem (Compound 1 or PF-03709270) resulted in significantly lower oral exposure of sulopenem in healthy human volunteers (AUC0–12 = 4.55 µg hr/ml at 500 mg dose; fed patients) [18] as compared to the oral exposure of tebipenem after administration of the TBPM-PI prodrug (AUC0-last = 21.4 µg hr/ml at 600 mg dose) [19]. Exposure to sulopenem can be improved by combining it with probenecid (AUC0–12 = 6.4 µg hr/ml). Recent clinical data from study IT001–102 reported AUC0–∞ = 3.87 µg hr/ml for 500 mg sulopenem etzadroxil prodrug and AUC0–∞ = 4.96 µg hr/ml for 500 mg sulopenem etzadroxil plus 500 mg probenecid [20]. It was also reported that results from clinical study IT001–101 showed that food increased the mean AUC and mean time above MIC for 500 mg sulopenem etzadroxil dosed with 500 mg probenecid on Day 1 by 62% and 68%, respectively [20]. Another oral treatment in development by Achaogen is a ceftibuten/clavulanate combination designated as C-scape [21]. A potential gap in bacterial spectrum compared with penems and carbapenems is lack of coverage of AmpC-producing isolates [22].
Treatment of urinary tract infections in the era of antimicrobial resistance and new antimicrobial agents
Published in Postgraduate Medicine, 2020
Mazen S. Bader, Mark Loeb, Daniela Leto, Annie A. Brooks
Sulopenem is a new broad-spectrum carbapenem in development in both oral and intravenous formulations for the treatment of uncomplicated and cUTIs. It has antimicrobial activity similar to other carbapenems except it has no activity against P. aeruginosa [97].