Clinical pharmacology of all-trans retinoic acid Conference Paper
| Authors: | Muindi, J. R. F.; Young, C. W.; Warrell, R. P. Jr |
| Title: | Clinical pharmacology of all-trans retinoic acid |
| Conference Title: | 2nd Workshop on Retinoids in Oncology |
| Abstract: | The clinical pharmacology of all-trans retinoic acid (RA) has distinct differences from that of its widely studied stereoisomer 13-cis retinoic acid (cRA). RA is much more rapidly cleared from plasma following oral administration; their respective half-lives are <1 h and 13 h. There is extensive accumulation of the 4-oxo-cRA in plasma following repeated doses of cRA, while 4-oxo-RA is only a minor metabolite in plasma following RA administration. The extent of isomerization in vivo differs for the two retinoids. In constrast to cRA, where up to a 1:3 ratio of RA to cRA is observed in patient plasma following drug administration, cRA concentrations in excess of 10 ng/ml are rarely observed in plasma of patients receiving exogenous RA. RA administration produces autoinduction of its own oxidative catabolism; this effect does not occur with cRA. These pharmacokinetic differences have been observed in leukemia and solid tumor patients. Detailed analysis of the results of the population studied suggest that both constitutive and RA-induced hypercatabolism of RA occurs. Both of these hypercatabolic states can be modulated by concurrent administration of ketoconazole, an inhibitor of cytochrome P-450 and lipoxygenase-mediated oxidations. |
| Keywords: | cancer chemotherapy; clinical article; controlled study; leukemia; clinical trial; area under the curve; solid tumor; conference paper; controlled clinical trial; multiple myeloma; lung non small cell cancer; prostate cancer; drug accumulation; lymphoma; drug clearance; drug metabolism; drug blood level; ketoconazole; drug half life; retinoic acid; drug oxidation; cis trans isomerism; cytochrome p450; oral drug administration; clinical pharmacology; lipoxygenase; human; priority journal |
| Journal Title | Leukemia |
| Volume: | 8 |
| Issue: | Suppl. 3 |
| Conference Dates: | 1994 Jan 21-22 |
| Conference Location: | London, United Kingdom |
| ISBN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1994-01-01 |
| Start Page: | S16 |
| End Page: | S21 |
| Language: | English |
| PUBMED: | 7808019 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
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