PHARMACOKINETIC AND CLINICAL STUDIES OF CEFTERAM PIVOXIL GRANULE IN THE PEDIATRIC FIELD

• Published in: Japanese journal of antibiotics 1989/09/25, Vol.42(9), pp.2023-2061
• Main Authors: MOTOHIRO, TAKASHI, YOSHINAGA, YOICHIRO, ODA, KEIKO, ARAMAKI, MASAFUMI, KAWAKAMI, AKIRA, TANAKA, KOICHI, KOGA, TATSUHIKO, TOMITA, SHOBUN, SAKATA, YASUTAKA, YAMASHITA, FUMIO, TAKAJO, NOBUHIKO, OKABAYASHI, SAYURI, SHIMIZU, TAKASHI, YAMADA, TAKASHI, OHBU, KEIZO, IMAI, SHOICHI, ARAKI, HISAAKI, TAKAHASHI, KOICHI, HARADA, HIROKO, KANEKO, SHINYA, YAMAMURA, JUNICHI, ISHIKAWA, YUTAKA, MATSUMOTO, KOJI, NAGAYAMA, KIYOTAKA, YASUOKA, CHIKAI, HAYASHI, MASAO, SHIMADA, YASUSHI, SHINDO, SHIZUO, NINOMIYA, MASAYUKI, MIHARA, SEIKO, AMAMOTO, MASANO, YAMAKAWA, RYOICHI, HASHIMOTO, NOBUO, TANAKA, NOBUO, KATO, EIJI, HARADA, YUTAKA, ISHIMOTO, KOJI, TAKAGI, JUNICHI, MORITA, JUN, NISHIYAMA, TOHRU, AIDA, KATSUMARO, SASAKI, HIROKAZU, OKI, SHINICHIRO, FUJISAWA, TAKUJI, TOMINAGA, KAORU, KOGA, TATSUO, KUBOTA, KAORU, KUDA, NAOKI, TSUGAWA, SHIN, KAMESAKI, KENJI, TANAKA, MOTOHISA, OHYAMA, KOTOKU, TAKASAKI, YOSHIO, YOSHINAGA, Yozo, KAWANO, NOBUHARU, TANAKA, CHIHEI, YOKOCHI, KAZUOKI, FUJIMOTO, TAMOTSU
• Format: Article
• Language: Japanese
• Subjects: Bacterial Infections - drug therapy; Cefmenoxime - analogs & derivatives; Cefmenoxime - pharmacokinetics; Cefmenoxime - pharmacology; Cefmenoxime - therapeutic use; Child; Child, Preschool; Drug Evaluation; Humans; Infant; Microbial Sensitivity Tests
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.42.2023

Cefteram pivoxil (CFTM-PI), the pivaloyloxymethyl ester of cefteram (CFTM) in which aminothiazol was also introduced into the 7 position of cephem nucleus, is a new oral cephem antibiotic. CFTM-PI was absorbed through the intestines and hydrolyzed to CFTM by esterases in the intestinal wall and existed in the body fluids as CFTM. A tablet form of this drug has been released in Japan and now a granular form for pediatric patients has been developed. We have determined MICs of 5 drugs (CFTM, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), erythromycin (EM)), against stock strains and MICs of 6 drugs (CFTM, CEX, CCL, ABPC, methicillin, cloxacillin) against fresh strains from patients received to CFTM-PI, with an inoculum size of 106 cfu/ml. A total of 149 strains included Gram-positive cocci i. e. Staphylococcus aureus (11), Streptococcus pyogenes (85), Streptococcus agalactiae (16) and Streptococcus pneumoniae (4), and Gram-negative rods i. e. Haemophilus influenzae (11), Bordetella pertussis (11), Escherichia coli (9), Proteus mirabilis (1) and Morganella morganii (1). The granular form of CFTM-PI was administered to 9 boys (age: 8 years 3 months-10years 10 months) to determine serum and urinary concentrations of the drug and its urinary recovery rates using bioassay. Doses of 1.5, 3.0 and 6.0mg/kg were given orally 30 minutes after meal to 3 boys, respectively. Urinary concentrations and its urinary recovery rates of T-2525A, a main metabolite of CFTM, were determined using high performance liquid chromatography (HPLC). To study clinical and bacteriological effects of this drug, a mean daily dose of 3.3mg/kg divided 3-4 times a day (3 times: 133 cases, 4 times: 9 cases) was administered for 8 days on the average to a total of 142 cases with pharyngitis (22), tonsillitis (12), acute bronchitis (3), pneumonia (11), pleurisy (1), scarlet fever (28), acute purulent otitis media (16), impetigo (13), abscess (2), purulent lymphadenitis (1) and urinary tract infection (33). Adverse reactions and abnormal effects on laboratory test values attributable to this drug were studied in patients. The results obtained are summarized as follows. 1. With regard to Gram-positive cocci, MICs of CFTM against 11 fresh strains of S. aureus ranged from 3.13 to 6.25μg/ml except for 1 strain, thus CFTM was equally effective to CEX, but less active than the other drugs tested. MIC90 of CFTM against 50 stock strains of S. pyogenes was 0.025μg/ml, hence CFTM was less active than