BASIC AND CLINICAL STUDIES ON S-1108 IN PEDIATRIC FIELD

• Published in: Japanese journal of antibiotics Vol. 46; no. 12; pp. 1122 - 1144
• Main Authors: MOTOHIRO, TAKASHI, HANDA, SHOICHI, YAMADA, SYUJI, OKI, SHINICHIRO, YOSHINAGA, YOICHIRO, ARAMAKI, MASAFUMI, ODA, KEIKO, SAKATA, YASUTAKA, KATO, HIROHISA, YAMASHITA, FUMIO, IMAI, SHOICHI, SUZUKI, KAZUSHIGE, OKABAYASHI, SAYURI, KANEKO, SHINYA, ICHIKAWA, KOTARO, SODA, HIROKO, SHIMIZU, TOKO, NAGATA, YOICHI, KIBA, MARIE, ISHIBASHI, SHINSAKU, TAKAHASHI, KOICHI, SUGIYAMA, AMIKO, MIYAKE, TAKUMI, ARAKI, HISAAKI, KAKISAKO, MITSUO, MAENO, YASUKI, SHIMOHIDA, TSUYOSHI, TAKAGISHI, TOMOYA, MATSUKUMA, YOSHINORI, HIRATA, TOMOSHIGE, TANAKA, NOBUO, NAGAYAMA, KIYOTAKA, YASUOKA, CHIKAI, HAYASHI, MASAO, AMAMOTO, MASANO, TSUMURA, NAOKI, ONO, EIICHIRO, KAMIZONO, SHINTARO, NAKASHIMA, EISUKE, NAGAMITSU, SHINICHIRO, NOMASA, TAKAYO, MATSUO, YUSAKU, HIGUCHI, EMI, NAGAI, KENSUKE, SUEYOSHI, KEIKO, HASHIMOTO, NOBUO, YUGE, KEN, KUBOTA, KAORU, KAWAKAMI, AKIRA, WATANABE, YORIKO, FUJISAWA, TAKUJI, NISHIYAMA, TORU, IWANAGA, RIKAKO, USHIJIMA, KOSUKE, YAMAKAWA, RYOICHI, YAMAMURA, JYUNICHI, TOMINAGA, KAORU, DAI, SYUNICHI, ANDO, HIROSHI, KUDA, NAOKI, FUJIMOTO, TAMOTSU, MOTOYAMA, HIROTAKA, MARUOKA, TAKAYUKI, DATE, YUKIJI, SUGIMURA, TORU, NISHIYORI, SUNAO, ASAKINO, YUKI, YAMADA, KATSUHIKO, KOREMATSU, SEIGO, HAYAKAWA, HIROSHI, SASAKI, HIROKAZU, KIMURA, KOICHI, YAMADA, TAKASHI
• Format: Journal Article
• Language: Japanese
• Published: Japan Japan Antibiotics Research Association 01.12.1993
• Subjects: Administration, Oral; Bacteria - drug effects; Bacterial Infections - drug therapy; Bacterial Infections - microbiology; Cephalosporins - administration & dosage; Cephalosporins - pharmacokinetics; Cephalosporins - pharmacology; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Male; Prodrugs - administration & dosage; Prodrugs - pharmacokinetics; Prodrugs - pharmacology
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.46.1122

S-1108 is a new oral esterified cephem antibiotic. Its active form, S-1006, has a broad antimicrobial spectrum against both Gram-positive and Gram-negative bacteria. Furthermore, S-1006 is extremely stable against β-lactamases with some exceptions. In the present study, we conducted laboratory and clinical evaluations of S-1108 granules in pediatrics. The obtained results are summarized as follows. 1. A drug sensitivity test revealed that MIC80, of the drug against 456 clinical isolates of Staphylococcus aureus that had been kept in our laboratory was 6.25μg/ml, similar to those of cefaclor (CCL) and methicillin (DMPPC). The most frequent MIC was 1.56μg/ml against 20 strains of S. aureus isolated from patients who received this drug, and this value was similar to those for CCL, amoxicillin (AMPC) and DMPPC. As regards to Streptococcus pyogenes, MIC of S-1006 was≤0.025μg/ml against 449 clinical isolates in our culture collection and 7 strains obtained from patients who received this drug, and these MICs are similar to those of cefteram (CFTM). MICs of S-1006 against 5 strains of Streptococcus pneumoniae obtained from patients who received this drug were≤0.025μg/ml, 0.10μg/ml or 0.39μg/ml which are similar to those of CFTM. MICs of S-1006 against 4 strains of Haemophilus influenzae obtained from patients who received this drug were 0.05 or 0.10μg/ml which are similar to those of CFTM. 2. When S-1108 granule preparation was administered to 1 patient at 4.0mg/kg, the peak plasma concentration of S-1006 was 1.25μg/ml. S-1108 granule preparation was also administered to 2 patients at 6.0mg/kg, and the peak plasma concentrations were 2.43μg/ml and 2.23μg/ml. Plasma half-lives were 1.11 hours after 4.0mg/kg and 1.28 hours in both patients given 6.0μg/ml. AUCs were 4.06, 8.37 and 7.73 μg·hr/ml, respectively. A dose-response relationship was observed between the two doses. 3. Urinary concentration was the highest during the 4-6-hour period for a patient given 4.0mg/kg, and during the 0-2-hour or 4-6-hour period for 2 patients given 6.0mg/kg. The peak concentrations were 25 8.0, 602.0 and 500.0μg/ml, respectively, and urinary recovery rates during the 0-8-hour period were 38.9, 38.3 and 23.1%, respectively. 4. Clinical effects were excellent or good in 88 of 93 patients, showing a very high efficacy rate of 94.6%. 5. As to the bacteriological effects 43 of 48 strains were eliminated, with an elimination rate of 89.6%. 6. Adverse reactions observed included dizziness in a patients and diarrhea in 2 patients (2.1%). 7. Laboratory tests revealed eosinophilia in 1 of 47 patients (2.1%) examined.