PHARMACOKINETICS OF ALL-TRANS-RETINOIC ACID IN JAPANESE PATIENTS WITHACUTE PROMYELOCYTIC LEUKEMIA

All-trans-retinoic acid (ATRA) was administered at 45 mg/m(2) to 4 Jap anese patients with acute promyelocytic leukemia (APL). A pharmacokine tic study revealed that the mean peak plasma concentration was 208 ng/ ml and was reached at 150 min after ingestion. The mean area under the concentration x time curve (AUC) was 498 ng . h/ml. Two patients show ed a good hematological response to ATRA, and they had higher peak pla sma concentrations of ATRA and larger AUCs. In one patient, dose escal ation of ATRA (90 mg/m(2)) increased the plasma concentration markedly . In another patient, the plasma concentration decreased markedly in t he fasting state. A larger pharmacokinetic study is necessary to exami ne the influence of food on the absorption of this agent and an optimu m administration schedule of ATRA in Japanese APL cases.