The urinary recovery and tolerability of FCE 22101, a broad spectrum injectable penem, were investigated in a multicentre single-blind randomized crossover study of 60 healthy male volunteers. Single 1 g doses of FCE 22101 or placebo were given by intravenous bolus at weekly intervals. FCE 22101 was given either after intake of 750 ml water (treatment A) or after 8 h of water restriction (treatment B). Placebo was given under water restriction (treatment C). Urine samples obtained at timed intervals were assayed for FCE 22101 and its metabolites P1 and P2 by HPLC. The 24 h urinary recoveries of the parent drug and its metabolites were similar after treatments A and B. Mean recoveries +/- S.D were 29 +/- 13% (FCE 22101), 31 +/- 12% (P1) and 7 +/- 2% (P2) of the dose. Transient suprapubic pain or dysuria, or both, were reported by two subjects after treatment A and by six subjects after treatment B. Symptoms were associated with low urine volumes at 0-2 h and low urinary recovery of FCE 22101 and metabolite P1.
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http://dx.doi.org/10.1093/jac/23.suppl_c.197 | DOI Listing |
Pharmacotherapy
November 2003
Department of Medical Microbiology, Royal Free and University College London Medical School, London, England.
Many beta-lactam antimicrobials were developed between the 1960s and 1980s, with continuing development driven by the emergence of microbial resistance. Penems form a discrete class of beta-lactams that comprises structural hybrids of penicillins (penams) and cephalosporins (cephems). The chemistry and microbiology of the representative penems MEN 10700, ritipenem, CGP 31608, sulopenem, BRL 42715, and faropenem are reviewed.
View Article and Find Full Text PDFAntimicrob Agents Chemother
July 2001
Department of Microbiology, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.
Pseudomonas aeruginosa exhibits high intrinsic resistance to penem antibiotics such as faropenem, ritipenem, AMA3176, sulopenem, Sch29482, and Sch34343. To investigate the mechanisms contributing to penem resistance, we used the laboratory strain PAO1 to construct a series of isogenic mutants with an impaired multidrug efflux system MexAB-OprM and/or impaired chromosomal AmpC beta-lactamase. The outer membrane barrier of PAO1 was partially eliminated by inducing the expression of the plasmid-encoded Escherichia coli major porin OmpF.
View Article and Find Full Text PDFJ Antibiot (Tokyo)
October 2000
CNR-ICOCEA, Bologna, Italy.
The synthesis and biological properties of the new penem antibiotic MEN 10700 (6) and of its selected oral prodrug MEN 11505 (8f) are described. MEN 10700 showed a broad spectrum of activity, with high potency both on Gram-positive and Gram-negative strains. It also exhibited good antibacterial activity toward anaerobes and on strains selected for their resistance to other antibacterial agents (cefotaxime- or ceftazidime-resistant Gram-negative strains, ciprofloxacin-resistant E.
View Article and Find Full Text PDFAntimicrob Agents Chemother
October 1999
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan.
Ritipenem is highly bacteriolytic against Haemophilus influenzae. Bacterial lysis was shown after treatments with ritipenem and cefsulodin at their MICs and after treatments with fropenem and cefdinir at four times their MICs, indicated by decreases in the culture turbidities and by morphological changes of the destroyed cells. These beta-lactams were preferentially bound to penicillin-binding protein (PBP) 1b.
View Article and Find Full Text PDFJ Pharm Biomed Anal
June 1998
Analytical Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
A sensitive high performance liquid chromatographic method for the simultaneous determination of an active metabolite (FCE22101) and open-ring metabolites (P1, P2) of a penem antibiotic, FCE22891, in dog plasma was developed. Plasma samples were pretreated only by ultrafiltration for the determination of the metabolites. The filtrates were directly analyzed by a reversed-phase high-performance liquid chromatographic system using a two-sided bracketing injection technique.
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