Intranuclear concentration measurements of doxorubicin in living leucocytes from patients treated for a lympho-proliferative disorder.
The accumulation of doxorubicin (DOX) in white blood cells of treated patients has been studied by quantitative microspectrofluorometry. From blood samples of treated patients, leucocyte subpopulations were separated by the gradient method. Emission fluorescence spectra from a microvolume of a single living cell nucleus were analysed in terms of spectral shape and fluorescence yield between free and DNA-bound doxorubicin. With this non-destructive analysis technique, intranuclear doxorubicin concentrations were determined within +/- 10%. Doxorubicin concentrations were measured in patients treated with bolus injection. After an accumulation of DOX in leucocytes during the first 30 min, intranuclear doxorubicin concentration did not vary significantly for 24 h, whereas its concentration in plasma decreased. Despite large differences between patients, monocytes accumulated significantly more doxorubicin than granulocytes or lymphocytes did.
Morjani
H
H
Laboratoire de Spectroscopie Biomoléculaire, GIBSA, UFR de Pharmacie, Reims, France.
Pignon
B
B
Millot
J M
JM
Debal
V
V
Lamiable
D
D
Potron
G
G
Etienne
J C
JC
Manfait
M
M
D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007834:Lasers; D007962:Leukocytes / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000188:drug therapy*; D009000:Monocytes / Q000378:metabolism; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy; D013050:Spectrometry, Fluorescence
D004317:Doxorubicin