Safety and carnitine status after oral administration of S-1108 to pediatric patients

Ryochi Fujii, Keisuke Sunakawa, Takao Yokota, Yasuko Nitta, Hironobu Akita, Satoshi Iwata, Yoshitake Satoh, Hidenori Meguro, Hajime Satoh, Kenji Niino, Yoshikiyo Toyonaga, Naoichi Iwai, Haruhi Nakamura, Yohnosuke Kobayashi, Minoru Kino, Hirohiko Higashino, Hitoshi Kamiya, Kenji Kitamura, Masao Ito, Takashi NishikawaHisayuki Tada, Akinori Maruo, Sadao Yamamoto

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2 Citations (Scopus)

Abstract

To investigate the clinical safety of S-1108, which contains pivalic acid, we measured both free carnitine, total carnitine and pivaloylcamitine in plasma and urine, and the acyl/free carnitine ratio in the plasma of pediatric patients (4-17 yrs) with pneumonia, bronchitis, and tonsillitis. The results are as follows: 1. Mean free and Total carnitine concentrations in the plasma of pediatric patients (n=120; male, 63; female, 57) untreated with S-1108 were 42.8±9.5 and 54.5±11.8 nmol/ml, respectively. 2. After the 4 to 12 days of treatment with daily dose of 6-18 mg/kg/day, free carnitine concentrations were reduced in all cases. The degree of free carnitine reduction depended on the dose and duration of S-1108 treatment. Free carnitine levels, however, showed a tendency to increase after the cessation of administration, and returned to normal within 3-4 days to about 7 days, at the lower and higher doses, respectively. Free carnitine concentrations in plasma were moderately reduced by 20% of pretreatment values at the highest doses, 16-18 mg/kg/day, however, there seemed to be full reversibility of carnitine status within a few days after cessation of treatment. 3. The acyl/free carnitine ratio, a parameter of secondary carnitine deficiency, was less than 0.5 in almost all cases during treatment, and there was no change in the ratio before, during and after S-1108 treatment. 4. No symptoms or adverse effects associated with carnitine deficiency were observed in any of the patients. Regarding carnitine status, S-1108 was demonstrated to be safe and well tolerated when administered at the recommended dosage schedule.

Original languageEnglish
Pages (from-to)655-665
Number of pages11
JournalChemotherapy
Volume41
Issue number6
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases
  • Pharmacology
  • Drug Discovery
  • Oncology

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    Fujii, R., Sunakawa, K., Yokota, T., Nitta, Y., Akita, H., Iwata, S., Satoh, Y., Meguro, H., Satoh, H., Niino, K., Toyonaga, Y., Iwai, N., Nakamura, H., Kobayashi, Y., Kino, M., Higashino, H., Kamiya, H., Kitamura, K., Ito, M., ... Yamamoto, S. (1993). Safety and carnitine status after oral administration of S-1108 to pediatric patients. Chemotherapy, 41(6), 655-665. https://doi.org/10.11250/chemotherapy1953.41.655