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 Kusumoto; Shiro 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

doi:10.11553/antibiotics1968b.42.953

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 language	English
Pages (from-to)	953-972
Number of pages	20
Journal	the japanese journal of antibiotics
Volume	42
Issue number	4
DOIs	https://doi.org/10.11553/antibiotics1968b.42.953
Publication status	Published - 1989
Externally published	Yes

All Science Journal Classification (ASJC) codes

Microbiology (medical)
Pharmacology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.11553/antibiotics1968b.42.953

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Fujii, R., Sakata, H., Inyaku, F., Fujita, K., Maruyama, S., Yoshioka, H., Hashira, S., Tajima, T., Nakazawa, S., Sato, H., Narita, A., Matsumoto, K., Nakazawa, S., Chikaoka, H., Kamigaki, M., Niino, K., Osano, M., Oikawa, T., Shiro, H., ... Suzuki, T. (1989). Pharmacokinetic and clinical evaluation of imipenem/cilastatin sodium in neonates and premature infants. the japanese journal of antibiotics, 42(4), 953-972. https://doi.org/10.11553/antibiotics1968b.42.953

@article{34c6464551d847bc8fb625251860da6e,

title = "Pharmacokinetic and clinical evaluation of imipenem/cilastatin sodium in neonates and premature infants",

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.",

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

year = "1989",

doi = "10.11553/antibiotics1968b.42.953",

language = "English",

volume = "42",

pages = "953--972",

journal = "the japanese journal of antibiotics",

issn = "0368-2781",

publisher = "Japan Antibiotics Research Association",

number = "4",

}

Fujii, R, Sakata, H, Inyaku, F, Fujita, K, Maruyama, S, Yoshioka, H, Hashira, S, Tajima, T, Nakazawa, S, Sato, H, Narita, A, Matsumoto, K, Nakazawa, S, Chikaoka, H, Kamigaki, M, Niino, K, Osano, M, Oikawa, T, Shiro, H, Kusumoto, Y, Azagami, S, Sunakawa, K, Ishizuka, Y, Hori, M, Toyonaga, Y, Sugita, M, Jo, K, Iwai, N, Taneda, Y, Nakamura, H, Nishimura, T, Tabuki, K, Aoki, S, Kobayashi, Y, Haruta, T, Okura, KE, Motohiro, T, Aramaki, M, Oda, K, Kawakami, A, Koga, T, Sakata, Y, Yamashita, F, Yura, J, Tsuruga, N, Kamiya, Y & Suzuki, T 1989, 'Pharmacokinetic and clinical evaluation of imipenem/cilastatin sodium in neonates and premature infants', the japanese journal of antibiotics, vol. 42, no. 4, pp. 953-972. https://doi.org/10.11553/antibiotics1968b.42.953

TY - JOUR

T1 - Pharmacokinetic and clinical evaluation of imipenem/cilastatin sodium in neonates and premature infants

AU - Fujii, Ryochi

AU - Sakata, Hiroshi

AU - Inyaku, Fumie

AU - Fujita, Kozo

AU - Maruyama, Shizuo

AU - Yoshioka, Hajime

AU - Hashira, Shintaro

AU - Tajima, Takeshi

AU - Nakazawa, Susumu

AU - Sato, Hajime

AU - Narita, Akira

AU - Matsumoto, Kimiko

AU - Nakazawa, Shinichi

AU - Chikaoka, Hidejiro

AU - Kamigaki, Masato

AU - Niino, Kenji

AU - Osano, Mitsuru

AU - Oikawa, Tadao

AU - Shiro, Hiroyuki

AU - Kusumoto, Yutaka

AU - Azagami, Shiro

AU - Sunakawa, Keisuke

AU - Ishizuka, Yugo

AU - Hori, Makoto

AU - Toyonaga, Yoshikiyo

AU - Sugita, Morimasa

AU - Jo, Kohsuke

AU - Iwai, Naoichi

AU - Taneda, Youichi

AU - Nakamura, Haruhi

AU - Nishimura, Tadafumi

AU - Tabuki, Kazuo

AU - Aoki, Shigeyuki

AU - Kobayashi, Yutaka

AU - Haruta, Tsunekazu

AU - Okura, Kan Etsu

AU - Motohiro, Takashi

AU - Aramaki, Masashi

AU - Oda, Keiko

AU - Kawakami, Akira

AU - Koga, Tatsuhiko

AU - Sakata, Yasutaka

AU - Yamashita, Fumio

AU - Yura, Jiro

AU - Tsuruga, Nobuatsu

AU - Kamiya, Yasuhiro

AU - Suzuki, Tatsuya

PY - 1989

Y1 - 1989

N2 - 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.

AB - 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.

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U2 - 10.11553/antibiotics1968b.42.953

DO - 10.11553/antibiotics1968b.42.953

M3 - Article

C2 - 2671429

AN - SCOPUS:0024605353

SN - 0368-2781

VL - 42

SP - 953

EP - 972

JO - the japanese journal of antibiotics

JF - the japanese journal of antibiotics

IS - 4

ER -

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

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