Pharmacokinetics of all-trans-retinoic acid administered on an intermittent schedule (Meeting abstract).

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Pharmacokinetics of all-trans-retinoic acid administered on an intermittent schedule (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 34:A1265 1993. Unique Identifier : AIDSLINE ICDB/93692235
Adamson PC; Balis FM; Yarchoan R; Pluda JM; Bailey J; Murphy RF; Bauza S; Poplack DG; Pediatric and Medicine Branches, NCI, Bethesda, MD 20892

Abstract: All-trans-retinoic acid (ATRA) is an effective agent for inducing complete remissions in patients (pts) with acute promyelocytic leukemia, but as a single agent, it does not appear able to maintain pts in remission. In pharmacokinetic (PK) studies of a chronic daily dosing schedule, systemic exposure to ATRA, as measured by the area under the plasma concentration-time curve (AUC), decreases dramatically over time. We have previously demonstrated that this disease results from induction of a capacity-limited elimination process for ATRA. The present study was performed to determine if an intermittent dosing schedule of ATRA allows for return of ATRA metabolism to baseline levels. Pts with HIV infection and Kaposi's sarcoma who were enrolled on a trial of intermittent ATRA received cycles consisting of 7 consecutive days of ATRA (40 mg/m2 tid) followed by 7 days off drug. PK monitoring was performed on days 1 and 7 of the first wk of treatment and again following the first dose after a 7-day interval off drug. The plasma AUC decreased from an av of 181 uM/min on days 1 to 15 uM/min by the 7th day of consecutive drug administration. Following a 7-day interval without drug, the plasma AUC increased to 231 uM/min. Peak plasma concentrations of ATRA diminished from an av of 1.45 uM on day 1 to 0.22 uM by day 7 of therapy, but returned to 1.85 uM following a 7-day interval off drug. A 7-day period off of ATRA appears sufficient to allow for return of plasma ATRA concentrations to baseline values. These results suggest that an intermittent schedule of ATRA has potential advantages over continuous administration.

Keywords: Drug Administration Schedule Human HIV Infections/*BLOOD/DRUG THERAPY Metabolic Clearance Rate/PHYSIOLOGY Sarcoma, Kaposi's/*BLOOD/DRUG THERAPY Skin Neoplasms/*BLOOD/DRUG THERAPY Tretinoin/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS ABSTRACT
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M9380833

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