Relationship between an effective dose of imatinib, body surface area, and trough drug levels in patients with chronic myeloid leukemia.
The standard dose of imatinib for the treatment of chronic-phase chronic myeloid leukemia (CML) is 400 mg/day. Some patients receive reduced doses of imatinib because of serious adverse effects. Recently, the effective plasma threshold for trough imatinib levels was demonstrated to be 1,002 ng/mL. In this study, we evaluated the association of an imatinib dose with trough plasma concentrations and clinical outcomes in 31 patients with chronic-phase CML who were treated at Kumamoto University Hospital. Twenty-seven patients were optimally treated with various doses of imatinib. The mean (+/-SD) trough plasma concentrations of imatinib were 1.40 +/- 0.57 microg/mL in 13 patients receiving 400 mg/day and 1.15 +/- 0.44 microg/mL in 9 patients receiving 300 mg/day as an effective dose. Mean trough levels of the two groups were not significantly different and exceeded the effective plasma threshold. Body surface area (BSA) was significantly smaller in patients receiving the reduced dose compared with those receiving the standard dose (p = 0.001). The effective imatinib dose was associated with age and gender as well as BSA. A reduced dose of 300 mg/day of imatinib may be sufficient for the treatment of CML patients with smaller body size, particularly when intolerability arises.
Kawaguchi
Tatsuya
T
Department of Hematology and Infectious Diseases, Kumamoto University Hospital, Kumamoto, Japan. tatsu@kumamoto-u.ac.jp
Hamada
Akinobu
A
Hirayama
Chie
C
Nakashima
Reiko
R
Nambu
Takeru
T
Yamakawa
Yuji
Y
Watanabe
Hiroshi
H
Horikawa
Kentaro
K
Mitsuya
Hiroaki
H
Saito
Hideyuki
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D001830:Body Surface Area; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D016896:Treatment Outcome; D055815:Young Adult
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate