Pharmacokinetic and clinical evaluation of imipenem/cilastatin sodium in neonates and premature infants

Ryochi Fujii, Hiroshi Sakata, Fumie Inyaku, Kozo Fujita, Shizuo Maruyama, Hajime Yoshioka, Shintaro Hashira, Takeshi Tajima, Susumu Nakazawa, Hajime Sato, Akira Narita, Kimiko Matsumoto, Shinichi Nakazawa, Hidejiro Chikaoka, Masato Kamigaki, Kenji Niino, Mitsuru Osano, Tadao Oikawa, Hiroyuki Shiro, Yutaka KusumotoShiro Azagami, Keisuke Sunakawa, Yugo Ishizuka, Makoto Hori, Yoshikiyo Toyonaga, Morimasa Sugita, Kohsuke Jo, Naoichi Iwai, Youichi Taneda, Haruhi Nakamura, Tadafumi Nishimura, Kazuo Tabuki, Shigeyuki Aoki, Yutaka Kobayashi, Tsunekazu Haruta, Kan Etsu Okura, Takashi Motohiro, Masashi Aramaki, Keiko Oda, Akira Kawakami, Tatsuhiko Koga, Yasutaka Sakata, Fumio Yamashita, Jiro Yura, Nobuatsu Tsuruga, Yasuhiro Kamiya, Tatsuya Suzuki

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Abstract

Pharmacokinetics and clinical studies of imipenem/cilastatin sodium (IPM/CS), a combined preparation of a new carbapenem antibiotic and a dehydropeptidase-I inhibitor, respectively, were carried out in neonates and premature infants in a joint study by a co-research group. 1. Peak blood levels of IPM/CS when administered at 10mg/10mg/kg or 20mg/20mg/kg by 30- or 60-minute intravenous drip infusion were achieved at the end of infusion. A dose response was clearly observed between the doses and the peak levels achieved. 2. The areas under the blood concentration time curve (AUC) of CS were greater than those of IPM in most patients. Blood half-lives of IPM and CS tended to be longer in younger neonates and premature infants than in older subjects. The blood half-life of CS tended to be longer than that of IPM. 3. Cumulative urinary recovery rates of CS were greater than those of IPM, cumulative urinary recovery rates tended to be greater in older neonates and premature infants than younger subjects. 4. One hundred and thirteen patients were treated for bacterial infections with IPM/CS and 32 patients were treated prophylactically. Daily doses of IPM/CS ranged from 9 mg/9 mg/kg to 150 mg/150 mg/kg. 5. Clinical efficacies of IPM/CS were evaluated in a total of 56 patients with identified etiologic pathogens. The efficacy rate was 9S.2% with 33 patients rated as excellent, 22 patients as good and 1 patient as fairly good. (Diagnoses were sepsis in 10 patients and meningitis in 2 patients, etc.) Fifty-seven patients with no identified etiologic pathogens were rated as excellent for 22 patients, good for 34 patients and fairly good for 1. The efficacy rate in these patients was 98.2%. Thirty-two patients were treated prophylactically and the results obtained were satisfactory. 6. Bacteriologically, the eradication rate was 94.5% in 56 patients; i.e., 52 were eradicated, 2 were decreased, 1 persisted and 1 was unknown. 7. Adverse effects were observed in 7 (4.4%) of 160 patients, i.e., 2 patients had diarrhea and 2 patients had rash, etc. Abnormal laboratory data considered related to the therapy occurred in 28 (17.6%) of 159 patients, with 10 patients with eosinophilia (6.3%) and elevation of GOT and/or GPT, etc. All these were non serious, and all values returned to normal after discontinuance of therapy. An abnormal prothrombin (PIVKA II) was observed in 1 of 10 patients tested. Accordingly, the dosage recommendation for IPM/CS in neonates and premature infants is as follows.

Original languageEnglish
Pages (from-to)953-972
Number of pages20
Journalthe japanese journal of antibiotics
Volume42
Issue number4
DOIs
Publication statusPublished - 1989
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

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