Cancer Chemotherapy and Pharmacology

, Volume 5, Issue 4, pp 243–249 | Cite as

A pharmacokinetic simulation model for chemotherapy of brain tumor with an antitumor protein antibiotic, neocarzinostatin

Theoretical considerations behind a two-compartment model for continuous infusion via an internal carotid artery
  • Hiroshi Maeda
  • Yoshinori Sano
  • Jiro Takeshita
  • Zenta Iwai
  • Hideyuki Kosaka
  • Tohru Marubayashi
  • Yasuhiko Matsukado
Original Articles Neocarzinostatin Brain Tumor Pharmacokinetic

Summary

A pharmacokinetic two-compartment model for the treatment of brain tumors in man was simulated with the aid of a computer. The parameters necessary for the simulations such as inactivation rate constant, elimination rate constant, distribution volume, blood volume, cerebral blood flow, and cytotoxic drug concentration were either determined in this study or obtained from the literature. A proteinaceous antitumor antibiotic, neocarzinostatin (NCS), was utilized as a prototype drug because it has features making it advantageous in the treatment of brain tumor. In particular, NCS has an extremely short half-life in serum (t1/2≤3s), while it is relatively stable in the cerebrospinal fluid (CSF) (t1/2∼50s). Therefore, the drug level in the cerebral compartment can be made adequately high with an appropriate infusion velocity into the cerebral compartment; however, it was possible to keep the plasma level of the drug much lower than the toxic level. Thus, few side-effects should result. In an in vitro study, NCS was found to exhibit its cytotoxicity to glioblastoma cells at a concentration as low as 0.005 μg/ml. In contrast, the cytotoxicity was not apparent for the normal glia cells at 0.1 μg/ml. The model being considered in this investigation is a two-compartment model, which consists of the cerebral compartment and the rest of the circulatory system of the body. In this case the drug is infused via an internal carotid artery. The results of pharmacokinetic simulation and dose regimens for NCS are presented, based on the effective concentration of the drug to glioblastoma cells in culture and the available pharmacological parameters.

Keywords

Brain Tumor Cerebral Blood Flow Internal Carotid Artery Glioblastoma Cell Elimination Rate Constant 

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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • Hiroshi Maeda
    • 1
  • Yoshinori Sano
    • 2
  • Jiro Takeshita
    • 1
  • Zenta Iwai
    • 3
  • Hideyuki Kosaka
    • 2
  • Tohru Marubayashi
    • 2
  • Yasuhiko Matsukado
    • 2
  1. 1.Department of MicrobiologyKumamoto University School of MedicineKumamotoJapan
  2. 2.Department of NeurosurgeryKumamoto University School of MedicineKumamotoJapan
  3. 3.Department of Mechanical Engineering, Faculty of EngineeringKumamoto UniversityKumamotoJapan

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