Table 1. Concentration of ritipenem in plasma, gallbladder tissue and bile after ritipenem acoxil administration (200 mg t.i.d., 3 days) N.D.: not det
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2 Table 1. Concentration of ritipenem in plasma, gallbladder tissue and bile after ritipenem acoxil administration (200 mg t.i.d., 3 days) N.D.: not detected *: time after last administration
3 Table 2. Concentration of ritipenem in plasma and gallbladder bile after ritipenem acoxil administration (400 mg. single D.o.) ND: not detected *: Combination of ursodeoxycholic acid (UDCA) at a dose of 200 mg : Hemodialysis for renal failure : Oral administration after breakfast
4 Table 3-1. Clinical results of ritipenem acoxil treatment in surgical infections
5 Table 3-2, Clinical results of ritipenem acoxil treatment in surgical infections
6 Table 3-3. Clinical results of ritipenem acoxil treatment in surgical infections MIC: Minimum inhibitory concentration Table 4. Clinical effect of ritipenem acoxil treatment in surgical infections coli, Streptococcus, Bacterides fragilis E.coli, Kiebsiella pneumoniae, Lactococeus lactis, Streptococcus morbillorum
7 334 OCT Table 5. Clinical effect of ritipenem acoxil according to dose Table 6. Bacteriological response to ritipenem acoxil treatment CNS: coagulase negative staphylococci
8 Table 7. Minimum inhibitory concentration of ritipenem for each bacterial strain isolated before and after treatment
9 Table 8. Correlation of MIC distribution of ritipenem (RIPM) and imipenem (IPM) for each bacterial strain isolated before and after treatment (n=25) Fig. 1. MIC distribution of ritipenem and other antibiotics for each bacterial strain isolated before and after treatment
10 4) Mitsuhashi S, Takagi S: In vitro antibacteri- al activity of FCE22101 and its stability toĈ 1) Franceschi G, Foglio M, Alpegiani M, Battistini C, Bedeschi A, Perrone E, Zarini F, Arcamone F, Della Bruna C, Sanfilippo A: Synthesis and biological properties of sodium Japan Sci, Soc. Press, Tokyo/Springer- Verlag, Berlin, 1991 lactamase. In Penem antibiotics (Mitsuhashi - S, Franceschi G ed.), p. 13 `39, Japan Sci. Soc. Press, Tokyo/Springer-Verlag, Berlin, ) Yokota T: Mode of action of penem antibiotics and their clinical significance. In Penem antibiotics (Mitsuhashi S, Franceschi G ed.), p. 43 `62, Japan Sci. Soc. Press, Tokyo/ Springer-Verlag, Berlin, ) Murakami K, Tanimura H, Ishimoto K, Ochiai M, Kesado T: Localization of dehydropeptidase-i in human tissues and hydrolysis of carbapenems in human terminal ileum. 18 th Intern Congr Chemother, Progr Abstr p. 255, 1993 (5R-6S-8R)-6a-hydroxyethyl-2-carbamoyloxymethyl-2-penem-3-carboxylate (FCE 22101)and its orally absorbed esters FCE22553 and FCE J Antibiot 36: 938 `941, ) Goto S, Miyazaki S : In vivo antimicrobial activity of FCE In Penem antibiotics (Mitsuhashi S, Franceschi Ged.), p.65 `76,
11 OCT Biliary excretion of ritipenem acoxil and its clinical efficacy in surgical infections Hiroshi Tanimura and Kazuhisa Uchiyama Department of Gastroenterological Surgery, Wakayama Medical School 27 Shichibancho, Wakayama 640, Japan Katsuyuki Ieda, Hiroshi Yukawa, Nakahiro Shimotsuma and Mitsuaki Minami Department of Surgery, Tonoda Hospital Yasuto Kobayashi, Shiro Terashita and Kiyofumi Johata Department of Surgery, Wakayama Rosai Hospital Masafumi Nakamura Department of Surgery, Hashimoto Municipal Hospital Masao Hashimoto and Yukitomo Sakamoto Department of Surgery, Hidaka General Hospital Shinji Yamamoto Department of Surgery, Kainan Municipal Hospital Shinji Iwakura Department of Surgery, Minami-Wakayama National Hospital Shinji Tani Department of Surgery, Nogami Kosei Hospital The kinetic profile and clinical efficacy of ritipenem acoxil (RIPM-AC), a new oral penem, were investigated. RIPM-AC was administered orally to 2 patients at dose of 200 mg t.i.d. for 3 days. At 2 `5 hours after the last administration before cholecystectomy, the gallbladder tissue concentration of ritipenem (RIPM), the active form of RIPM-AC, was not detectable. The concentrations in gallbladder bile were 0.12 and 0.64ƒÊg/ml, respectively. RIPM-AC was administered orally to 7 patients undergoing biliary drainage at a single dose of 400 mg. The maximum plasma concentration was ƒêg/ml at 1 `2 hours after administration, and the maximum bile concentration was 0.10 `47.3 ƒêg/ml at 1 `4 hours. RIPM-AC was administered to 31 patients with surgical infections at doses of mg t.i.d. for 3 `9 days. The clinical efficacy was excellent in 9, good in 18 and fair in 4, with the efficacy rate being 87.1%. The bacteriological efficacy rates were 93.8% (15/16) in Gram-positive bacteria, 80.0% (20/25) in Gram-negative bacteria and 100% (18/18) in anaerobic bacteria. As side effects, diarrhea was noted in 1 case, and liver function test values were elevated in 2 cases.
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