[Immobilized forms of daunorubicin in patients with acute leukemia].
OBJECTIVE
To study pharmacokinetics of liposomal daunorubicine DaunoXome and daunorubicine (rubomycin) associated with red cells: to assess their effectiveness and toxicity in patients with acute leukemia.


METHODS
7 patients with resistant or recurrent acute leukemia entered the trial. Of them 2 patients had acute myeloid leukemia. They received DaunoXome in dose 100 mg in days 1, 2 and 3 of 7 + 3 program. 1 patient had pretreated acute promyelocytic leukemia. This patient received 5-day course of DaunoXome in a dose 100 mg in the presence of ATRA therapy. 4 patients were given single dose daunorubicin associated with autoerythrocytes in the courses RACOP and 7 + 3 in a dose 45 mg/m2. Concentrations of free, bound and liposomal daunorubicin were determined spectrofluorimetrically in chlorophorm extracts of plasm, blood, liquor and bone marrow specimens.


RESULTS
Immobilization of daunorubicin on the red cells and liposomes changes pharmacokinetics of the drug: peak concentrations change and the area under the concentration curve increases. Tolerance of DaunoXome and daunorubicine associated with red cells was satisfactory in all the cases: clinical and echo-CG signs of cordiotoxicity were absent, myelotoxicity was similar to that of free daunorubicine. DaunoXome was effective in 2 of 3 patients with acute myeloblastic leukemia.


CONCLUSIONS
The findings are of practical interest for physicians designing new programs of therapy of acute leukemia.
Isaev
V G
VG
Garmaeva
T Ts
TTs
Skorokhod
A A
AA
Parovichnikova
E N
EN
Tiurina
N G
NG
Kucher
R A
RA
Vitvitskiĭ
V M
VM
Ataullakhanov
F I
FI
Savchenko
V G
VG
D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism; D003630:Daunorubicin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004337:Drug Carriers; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000378:metabolism*; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012074:Remission Induction; D013050:Spectrometry, Fluorescence
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D003630:Daunorubicin