EFFECT OF TAMOXIFEN ON THE PHARMACOKINETICS OF DOXORUBICIN IN PATIENTS WITH NON-HODGKINS-LYMPHOMA

The authors examined the effect of tamoxifen (TAM), a multiple-drug re sistance modulator, on the pharmacokinetics of doxorubicin (DOX) In pa tients with non-Hodgkin's lymphoma treated according to the CHOP-proto col which included DOX, cyclophosphamide, vincristine, and prednisone. The dose of DOX was 50 mg/ m(2), but was reduced 25% if the patient w as older than 60 years. Of these, 10 randomly-selected patients receiv ed a daily dose of 480 mg of TAM (Group-1) and 10 others did nor (Grou p-2). Blood samples were collected at different time intervals, and DO X was measured in plasma by liquid chromatography. The concentration-t ime data of DOX exhibited the characteristics of the two-compartment o pen model well. The mean (SEM) values of alpha, beta, k(12), k(21), k( 10), V-c, V-ss, AUG, total clearance, and mean residence time observed in Group-1 were 4.06 (0.96) h(-1), 0.0395 (0.0068) hr(-1), 3.13 (0.79 ) hr(-1), 0.264 (0.052) hr(-1), 0.708 (0.19) hr(-1), 525 (156) l/m(2), 1060 (163) l/m(2), 1145 (234) mu g.hr/l, 49.3 (8.5) l/hr.m(2), and 26 .8 (6.6) hours, respectively. Those in Group-2 were 4.99 (1.13) hr(-1) , 0.0432 (:0.0073) hr(-1), 2.46 (0.63) hr(-1), 0.111 (0.026) hr(-1), 2 .46 (0.86) hr(-1), 231 (53) l/m(2), 812 (149) l/m(2), 1690 (276) mu g. hr/l, 30.3 (4.1) l/hr.m(2), and 29.7 (5.1) hours, respectively. Of the se parameters, the difference between the two groups was significant ( p less than or equal to 0.0169) only in k(21). Thus, the coadministrat ion oi: TAM at the earlier-mentioned dose appears generally to have no significant influence on the pharmacokinetics of doxorubicin when use d in the CHOP-protocol.