长期α干扰素治疗对急性早幼粒细胞白血病中全反式维甲酸药代动力学的调节作用。

Modulation of all-trans retinoid acid pharmacokinetics in acute promyelocytic leukaemia by prolonged interferon-alpha therapy.

作者信息

Lazzarino M, Corso A, Regazzi M B, Iacona I, Bernasconi C

机构信息

Institute of Haematology, University of Pavia, Italy.

出版信息

Br J Haematol. 1995 Aug;90(4):928-30. doi: 10.1111/j.1365-2141.1995.tb05217.x.

DOI:10.1111/j.1365-2141.1995.tb05217.x

PMID:7669674

Abstract

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.

摘要

全反式维甲酸（ATRA）持续治疗会诱导药物代谢加速，这被认为是导致对ATRA产生获得性耐药的原因。我们研究了α-2a干扰素（IFN）对两名急性早幼粒细胞白血病（APL）患者ATRA药代动力学的影响，这两名患者处于完全缓解期，通过交替使用15天的IFN和15天的ATRA来维持病情。在IFN + ATRA治疗期间获得的第15天ATRA水平显著高于仅接受ATRA维持治疗的患者所观察到的水平。在一名患者中停用IFN后，第15天的ATRA水平降至仅计划接受ATRA维持治疗的患者所观察到的水平。在我们的两名患者中，IFN显著降低了ATRA分解代谢的诱导，表明IFN在调节ATRA药代动力学方面具有潜在作用。