Modulation of all-trans retinoid acid pharmacokinetics in acute promyelocytic leukaemia by prolonged interferon-alpha therapy.
Continuous treatment with all-trans retinoid acid (ATRA) induces accelerated drug catabolism which is considered responsible for acquired resistance to ATRA. We studied the effect of interferon-alpha 2a (IFN) on ATRA pharmacokinetics in two patients with acute promyelocytic leukaemia (APL) in complete remission maintained by alternating 15 d of IFN and 15 d of ATRA. Day 15 ATRA levels obtained during IFN+ATRA treatment were significantly higher than those observed in patients maintained on ATRA alone. In one patient IFN was discontinued and day 15 ATRA levels decreased to those observed in patients scheduled for maintenance with ATRA alone. In our two patients IFN substantially reduced the induction of ATRA catabolism, indicating a potential role for IFN in modulating ATRA pharmacokinetics.
Lazzarino
M
M
Institute of Haematology, University of Pavia, Italy.
Corso
A
A
Regazzi
M B
MB
Iacona
I
I
Bernasconi
C
C
D004347:Drug Interactions; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000378:metabolism / Q000627:therapeutic use*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000628:therapy; D011994:Recombinant Proteins; D014212:Tretinoin / Q000493:pharmacokinetics*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014212:Tretinoin