Pharmacokinetic study of temozolomide on a daily-for-5-days schedule in Japanese patients with relapsed malignant gliomas: first study in Asians

Int J Clin Oncol. 2007 Oct;12(5):341-9. doi: 10.1007/s10147-007-0687-5. Epub 2007 Oct 22.


Background: Temozolomide (TMZ) is widely used in Europe and the United States. For the safe use of TMZ in the Japanese, as representative of Asians, the pharmacokinetics of TMZ was investigated in Japanese patients and compared to that in Caucasians.

Methods: The pharmacokinetics and safety of TMZ following oral administration of 150 and 200 mg/m2 per day for the first 5 days of a 28-day treatment cycle were investigated in six Japanese patients with relapsed gliomas.

Results: The time-to-maximum plasma concentration (tmax) of TMZ was about 1 h and the elimination half-life of terminal excretion phase (t 1/2lambda z) was about 2 h. A dose-dependent increase was observed in maximum plasma concentration (Cmax) and AUC, while values for t 1/2lambda z, apparent total body clearance (CL/F), and apparent distribution volume (Vz/F) were independent of dose. After administration for 5 days, changes in pharmacokinetics and accumulation were not observed. The plasma 5-(3-methyl)1-triazen-1-yl-imidazole-4-carboxamide (MTIC) concentration changed in parallel with the TMZ plasma concentration, and the Cmax and AUC of MTIC were about 2% of those of TMZ. The pharmacokinetic parameters of TMZ and MTIC in Japanese patients in this study were comparable to those previously determined in Caucasian subjects. Adverse events occurred in all patients, but toxicities were mostly mild or moderate, and continuation of administration was possible by adjusting the dose and by delaying the start of the next treatment cycle.

Conclusion: The pharmacokinetic and safety profile of TMZ in Japanese patients was comparable to that in Caucasians. The treatment regimen used in Europe and the United States will be suitable for Asian patients, including Japanese.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / pharmacokinetics*
  • Area Under Curve
  • Asians
  • Brain Neoplasms / metabolism*
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / blood
  • Dacarbazine / pharmacokinetics
  • Drug Administration Schedule
  • Female
  • Glioma / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism*
  • Prognosis
  • Temozolomide
  • Whites


  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • 5-(3-methyl-1-triazeno)imidazole-4-carboxamide
  • Temozolomide