STUDIES ON THE CLINICAL PHARMACOKINETICS OFALL-TRANS RETINOIC ACID
Qi Xiaoqing ;Miao Jinming; Fang Zhiwen;et al(Rei Jin Hospital, Shanghai Second Medical Universijy,Shanghai, 200001)
he oharmacokinetics of all-trans-retinoic acid (A-TRA) was studied in four acute prornyelocytic leukemiapatients. ATRA was administered in a single oral doseof 80mg on the first day of treatment. The plasrna con-centration of ATRA was quantivated by reversed-phasehigh performance liquid chromatography. The time topeak concentrations of plasma ATRA was between 1. 6and 2. 8 h after administration with a maximum between158 and 300ng/ml. The clearance half-life ranged from41. 1 to 1. 8 h. Continued administration of ATRA re-sulted in a significant decrease in both the plasma peaklevels and the areas under the concentration time curveand a marked increase of clearance rates. The pharma-cokinetics of ATRA was also studied in four healthy vol-unteers. The drug was administered in a single dose of50mg. The T peak was from 15 to 2.1 with a cpmaxbetween 88～ 163ng/ml and t1/2 β between 1.0～ 1. 6h. The pharmacokinetics of ATRA in APL patients wasof no significant difference from that in healthy volun-teers. In patients with APL or other types of leukemia,the basic levels of endogenous retinol and retinoids inplasma were all within the ranges of that in controls (P 0. 05 ). These data suggested that the clinical ″ resis-tance″, of ATRA during continuous oral administrationmight be associated with the gradual decreasing of peaklevels and increasing of clearance rates .This will behelpful improving the clinical adrninistration scheme inAPL therapy.