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


CONCLUSIONS
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.
Aoki
Tomokazu
T
Department of Neurosurgery, Kitano Hospital Medical Research Institute, 2-4-2 Ogimachi, Kita-ku, Osaka 530-8480, Japan. tomokazu@kitano-hp.or.jp
Nishikawa
Ryo
R
Mizutani
Tomohiko
T
Nojima
Kuniharu
K
Mishima
Kazuhiko
K
Adachi
Jyunichi
J
Matsutani
Masao
M
D000284:Administration, Oral; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D001932:Brain Neoplasms / Q000378:metabolism*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011379:Prognosis; D000077204:Temozolomide; D044465:White People
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; C010243:5-(3-methyl-1-triazeno)imidazole-4-carboxamide; D000077204:Temozolomide