Pharmacokinetics of all-trans-retinoic acid administered on an intermittent schedule
| Autor: | J Bailey, James M. Pluda, Peter C. Adamson, S Bauza, Robert Yarchoan, Frank M. Balis, David G. Poplack, Robert F. Murphy |
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| Rok vydání: | 1995 |
| Předmět: |
Drug
Adult Cancer Research medicine.medical_treatment media_common.quotation_subject Tretinoin Pharmacology High-performance liquid chromatography Drug Administration Schedule Pharmacokinetics Leukemia Promyelocytic Acute Drug tolerance Oral administration medicine Humans Sarcoma Kaposi Chromatography High Pressure Liquid media_common Chemotherapy Acquired Immunodeficiency Syndrome Dose-Response Relationship Drug business.industry Remission Induction Half-life Drug Tolerance Middle Aged Up-Regulation Dose–response relationship Oncology business Half-Life |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 13(5) |
| ISSN: | 0732-183X |
| Popis: | PURPOSE Administration of all-trans-retinoic acid (ATRA) on a continuous daily schedule results in a rapid and sustained decrease in plasma drug concentrations. This pharmacokinetic study was performed to determine if administration of ATRA on an intermittent schedule could overcome the rapid decrease in plasma drug concentration and provide repetitive periods of higher plasma drug exposure. MATERIALS AND METHODS ATRA was administered on repetitive cycles of 7 consecutive days of drug followed by 7 days without drug. On the days of pharmacokinetic monitoring, following an overnight fast, a fixed single oral dose of 40 mg/m2 was administered and frequent plasma samples were obtained over 8 hours. Patients had pharmacokinetic studies performed on the first and seventh days of the first week, and on the first day of the third and eleventh weeks. ATRA was measured in plasma with a reverse-phase high-performance liquid chromatography (HPLC) assay. RESULTS Plasma exposure to ATRA as measured by the area under the plasma concentration-time curve (AUC) decreased significantly during the first week of drug administration, from a mean of 145 +/- 26 mumol/L.min on day 1 to 18 +/- 4 mumol/L.min by day 7. Plasma ATRA concentrations at the start of weeks 3 and 11 of this every-other-week schedule were equivalent to those achieved on day 1 of treatment, with mean AUCs of 177 +/- 39 and 128 +/- 30 mumol/L.min, respectively. CONCLUSION An intermittent schedule of ATRA administration results in repetitive periods of exposure to concentrations of ATRA normally only observed on the first day of treatment. Phase II trials to evaluate the role of intermittent schedules of administration for ATRA are planned. |
| Databáze: | OpenAIRE |
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